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 (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...

. 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 1883 ...

(1859–1921) in 1886 The reaction is a type of

electrophilic aromatic substitution Electrophilic aromatic substitution (SEAr) is an organic reaction in which an atom that is attached to an aromatic ring, aromatic system (usually hydrogen) is replaced by an electrophile. Some of the most important electrophilic aromatic substitut ...

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 In chemistry, a phosphoric acid, in the general sense, is a phosphorus acid, phosphorus oxoacid in which each phosphorus (P) atom is in the oxidation state +5, and is chemical bond, bonded to four oxygen (O) atoms, one of them through a double b ...

(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 reaction occurs. A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage ...

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

aniline Aniline (From , meaning ' indigo shrub', and ''-ine'' indicating a derived substance) is an organic compound with the formula . Consisting of a phenyl group () attached to an amino group (), aniline is the simplest aromatic amine. It is an in ...

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. 2007, 72, 9761–9764 revised the reaction mechanism showing that based on

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...

and theoretical calculations an O,O-dicationic intermediate (a superelectrophile) is favored comparing to the N,O dicationic intermediate. For preparative purposes triflic acid is recommended:

References

{{Reflist Quinoline forming reactions Name reactions