The Knorr quinoline synthesis is an intramolecular

organic reaction Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...

converting a β-ketoanilide to a 2-hydroxyquinoline using

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...

. This reaction was first described by

Ludwig Knorr Ludwig Knorr (2 December 1859 – 4 June 1921) was a German chemist. Together with Carl Paal, he discovered the Paal–Knorr synthesis, and the Knorr quinoline synthesis and Knorr pyrrole synthesis are also named after him. The synthesis in 18 ...

(1859–1921) in 1886 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. 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 In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...

identified a N,O-dicationic intermediate A with excess acid capable of ring-closing and a monocationic intermediate B which fragments to

aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine In organic chemistry, an aromatic amine is an organic compound consisting of an aroma ...

and (ultimately to) acetophenone. Aniline reacts with another equivalent of benzoylacetanilide before forming the 4-hydroxyquinoline. A 2007 study''Knorr Cyclizations and Distonic Superelectrophiles'' Kiran Kumar Solingapuram Sai, Thomas M. Gilbert, and Douglas A. Klumpp

J. Org. Chem. ''The Journal of Organic Chemistry'', colloquially known as ''JOC'', is a peer-reviewed scientific journal for original contributions of fundamental research in all branches of theory and practice in organic and bioorganic chemistry. It is publ ...

2007, 72, 9761–9764 revised the reaction mechanism and based on

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...

and theoretical calculations favors an O,O-dicationic intermediate (a

superelectrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries ...

) over the N,O dicationic intermediate . For preparative purposes triflic acid is recommended:

References

{{Reflist Quinoline forming reactions Name reactions