Willgerodt reaction

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The Willgerodt reaction is a name reaction of organic chemistry that was developed by the German chemist Conrad Willgerodt (1841–1930). In 1923, Karl Kindler (1891-1967) improved the process, and so the reaction became known as the Willgerodt-Kindler reaction .

Overview reaction

The Willgerodt reaction describes the synthesis of a carboxylic acid from an alkyl aryl ketone . In the simplest case, acetophenone is oxidized to phenylacetic acid:

Reaction scheme Willgerodt reaction

In the Willgerodt reaction, aqueous ammonium polysulphide solution is used as the oxidizing agent ; generally work is done under pressure. The number of carbon atoms remains unchanged. The carbonyl group of the reaction product is always positioned at the end of the alkyl chain. For example, the phenyl ethyl ketone Ph – CO – CH 2 –CH 3 produces the carboxylic acid Ph – CH 2 –CH 2 –COOH. Similarly, the carboxylic acid Ph-CH 2 -CH 2 -CH 2 -COOH is formed from phenyl ketone Ph-CO-CH 2 -CH 2 -CH 3 .

In the variant described by Kindler ( Willgerodt-Kindler reaction ), a mixture of elemental sulfur and a secondary amine is used instead of the ammonium polysulphide solution . The secondary amine can also be replaced by a primary amine or by ammonia . Due to Kindler's improvement of the process, it is possible to work without pressure.

Carboxylic acid derivatives as reaction products

Depending on how the reaction is carried out, carboxylic acid amides (X = O, Willgerodt reaction ) or carboxylic acid thioamides (X = S, Willgerodt-Kindler reaction ) can also be prepared instead of the carboxylic acids :

Reaction scheme for the formation of amides or thionamides

The radical R on the nitrogen atom usually stands for an organyl group (e.g. alkyl group).

mechanism

The mechanism of the reaction is not yet fully understood. Since the Willgerodt-Kindler reaction is only a modification of the Willgerodt reaction, both methods can be described with the same mechanism. This will be discussed using the example of phenylacetic acid ( 5 ) from acetophenone ( 1 ): First, the ketone 1 reacts with a secondary amine to form an enamine 2 . Due to an electrophilic attack on the part of the sulfur, the sulfur attaches to the enamine. After several rearrangements of electron pair bonds and intramolecular migrations of the acidic hydrogen atoms, a thioamide 3 is formed , which hydrolyses to the carboxylic acid 5 via the acid amide 4 .

Mechanism of the Willgerodt-Kindler reaction

However, this mechanism only explains the possible course of the reaction in the case of aryl methyl ketones. The formation of terminal carboxylic acids from ketones with higher alkyl groups cannot be explained in this way.

Similar reactions

The three-component reaction of primary amines, aromatic aldehydes and sulfur forms thioamides of aromatic carboxylic acids.

Individual evidence

  1. ↑ Conrad Willgerodt: About the action of yellow ammonium sulfur on ketones and quinones . In: Reports of the German Chemical Society . tape 20 , no. 2 , 1887, p. 2467-2470 , doi : 10.1002 / cber.18870200278 .
  2. ↑ Conrad Willgerodt: conversion of ketones and aldehydes into acids and acid amides by means of yellow ammonium sulphide . In: Reports of the German Chemical Society . tape 21 , no. 1 , 1888, p. 534-536 , doi : 10.1002 / cber.18880210195 .
  3. ↑ FW Euler , H. Jaeger, H. Jäger-Suhstenau, H. Körner, F. Menges, M. Otto, HJ Rieckenberg, F. Wagner, H. Walter: New German Biography . tape 11 . Duncker & Humblot, Berlin 1977, p. 619-620 .
  4. ↑ Karl Kindler: Studies on the mechanism of chemical reactions. First treatise. Reduction of amides and oxidation of amines . In: Justus Liebig's Annals of Chemistry . tape 431 , no. 1 , 1923, pp. 187-230 , doi : 10.1002 / jlac.19234310111 .
  5. ↑ a b Heinz GO Becker, Werner Berger, Günter Domschke, Egon Fanghänel , Jürgen Faust, Mechthild Fischer, Fritjof Gentz, Karl Gewald, Reiner Gluch, Roland Mayer , Klaus Müller, Dietrich Pavel, Hermann Schmidt, Karl Schollberg, Klaus Schwetlick, Erika Seiler, Günter Zeppenfeld, Rainer Beckert, Wolf D. Habicher, Hans-Joachim Knölker and Peter Metz: Organikum , 23rd edition, Wiley-VCH Verlag, 2009, ISBN 978-3-527-32292-3 , pp. 431-434 .
  6. ↑ a b Jerry March: Advanced Organic Chemistry , 3rd Edition, John Wiley & Sons, New York, 1985, ISBN 0-471-88841-9 , pp. 1566-1567.
  7. ↑ T. Laue and A. Plagens: Name and Keyword Reactions of Organic Chemistry , 5th Edition, Teubner Study Books Chemistry, 2006, ISBN 978-3-8351-0091-6 , pp. 342-344.
  8. ↑ T. Laue and A. Plagens: Name and Keyword Reactions of Organic Chemistry , 5th Edition, Teubner Study Books Chemistry, 2006, ISBN 978-3-8351-0091-6 , p. 343.
  9. ^ A b Hans Beyer and Wolfgang Walter : Organische Chemie , S. Hirzel Verlag, Stuttgart 1984, ISBN 3-7776-0406-2 , p. 546.
  10. ↑ Hualong Xu, Hang Deng, Zhengkai Li, Haifeng Xiang, Xiangge Zhou: Synthesis of Thioamides by Catalyst-Free Three-Component Reactions in Water , Eur. J. Org. Chem. 2013, pp. 7054-7057, doi: 10.1002 / ejoc.201301148 .