Ortoleva-King reaction

The Ortoleva-King reaction is a name reaction of organic chemistry , the discovery of which can be traced back to Giovanni Ortoleva in 1899 and which was taken up and further investigated by L. Carroll King in 1944. This synthesis can be used to prepare useful pyridinium iodide salts.

Overview reaction

In the Ortoleva-King reaction, the functional methyl or methylene group of an organic substance 1 reacts with iodine and two equivalents of pyridine 2 with the aid of heat to form the corresponding pyridinium iodide 3 and the pyridinium hydroiodide salt 4 . Of the organic radicals R ¹ and R ² in 1 , at least one is electron-withdrawing . These are responsible for the activation of the methylene group and ensure that the carbon-hydrogen bond of this methylene group is acidic.

General

Instead of pyridine , which is not only a starting material but also the solvent in this reaction, quinolines , isoquinolines, picolines and nicotinamides can also be used. The reaction takes place under the action of heat.

Reaction mechanism

The reaction mechanism of the reaction could be as follows. In the first step, the CH-acidic methylene group of molecule 1 is deprotonated by pyridine 2 . The pyridinium ion 3 and the anion 4 are formed .

Activation of a second equivalent of pyridine 2 with iodine 5 results in intermediate 6 .

The intermediate 6 is nucleophilically attacked by the anion 4 . The pyridinium iodide 7 is formed .

The recombination of the pyridinium ion 3 with the iodide produces the pyridinium hydroiodide salt 8 as a by-product.

application

Many different pyridinium iodide salts can be obtained using this method. The yield here depends heavily on the raw material used, but is generally very large. A problem with this reaction is the separation of the products, which means that losses in the yield must be expected. Even today, the Ortoleva-King reaction is still used in various synthesis processes.

Individual evidence

↑ ^a ^b ^c Jie Jack Li: Name Reactions in Heterocyclic Chemistry II . In: Wiley Series on Comprehensive Name Reactions . 6th edition. John Wiley & Sons, Inc., New Jersey 2011, ISBN 978-1-118-09282-8 , pp. 645-650 , doi : 10.1002 / 9781118092828 .
^ L. Carroll King: The Reactions of Iodine with Some Ketones in the Presence of Pyridine . In: Journal of the American Chemical Society . tape 66 , no. 6 , 1944, pp. 894–895 , doi : 10.1021 / ja01234a015 .
^ L. Carroll King, Margaret Mcwhirter: The Reactions of Acetophenone and Iodine with Some Nitrogenous Bases 1 . In: Journal of the American Chemical Society . tape 68 , no. 4 , April 1946, p. 717–717 , doi : 10.1021 / ja01208a504 .
↑ Anton J. Stasyuk, Marzena Banasiewicz, Michał K. Cyrański, Daniel T. Gryko: Imidazo [1,2-a] pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva – King Reaction . In: The Journal of Organic Chemistry . tape 77 , no. 13 , 2012, p. 5552-5558 , doi : 10.1021 / jo300643w .

[:0-1] Jie Jack Li: Name Reactions in Heterocyclic Chemistry II . In: Wiley Series on Comprehensive Name Reactions . 6th edition. John Wiley & Sons, Inc., New Jersey 2011, ISBN 978-1-118-09282-8 , pp. 645-650 , doi : 10.1002 / 9781118092828 .

[:3-2] L. Carroll King: The Reactions of Iodine with Some Ketones in the Presence of Pyridine . In: Journal of the American Chemical Society . tape 66 , no. 6 , 1944, pp. 894–895 , doi : 10.1021 / ja01234a015 .

[:1-3] L. Carroll King, Margaret Mcwhirter: The Reactions of Acetophenone and Iodine with Some Nitrogenous Bases 1 . In: Journal of the American Chemical Society . tape 68 , no. 4 , April 1946, p. 717–717 , doi : 10.1021 / ja01208a504 .

[:2-4] Anton J. Stasyuk, Marzena Banasiewicz, Michał K. Cyrański, Daniel T. Gryko: Imidazo [1,2-a] pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva – King Reaction . In: The Journal of Organic Chemistry . tape 77 , no. 13 , 2012, p. 5552-5558 , doi : 10.1021 / jo300643w .