Willgerodt rearrangement
{{Reactionbox
| Name = Willgerodt rearrangement
| Type = Rearrangement reaction
| NamedAfter = Conrad Willgerodt
| Section3 = {{Reactionbox Identifiers
| RSC_ontology_id = 0000185
}}
}}
The Willgerodt rearrangement or Willgerodt reaction is an organic reaction converting an aryl alkyl ketone, alkyne, or alkene to the corresponding amide by reaction with ammonium polysulfide, named after Conrad Willgerodt.{{cite journal |last1=Willgerodt |first1=Conrad |title=Ueber die Einwirkung von gelbem Schwefelammonium auf Ketone und Chinone |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1887 |volume=20 |issue=2 |pages=2467–2470|doi=10.1002/cber.18870200278|url=https://zenodo.org/record/1425499 }}{{cite journal |last1=Willgerodt |first1=Conrad |title=Ueberführung von Ketonen und Aldehyden in Säuren und Säureamide mittelst gelben Schwefelammoniums |journal=Berichte der Deutschen Chemischen Gesellschaft |date=1888 |volume=21 |issue=1 |pages=534–536 |doi=10.1002/cber.18870200278|url=https://zenodo.org/record/1425499 }}{{cite journal |last1=Carmack |first1=Marvin |last2=F. DeTar |first2=DeLos |title=The Willgerodt and Kindler Reactions. III. Amides from Acetylenes and Olefins; Studies Relating to the Reaction Mechanisms |journal=Journal of the American Chemical Society |date=1946 |volume=68 |issue=10 |pages=2029–2033 |doi=10.1021/ja01214a048}}{{cite journal |last1=Carmack |first1=Marvin |last2=Spielman |first2=M. A. |title=The Willgerodt Reaction |journal=Organic Reactions |date=1946 |volume=3 |pages=83–107 |doi=10.1002/0471264180.or003.02 |isbn=9780471005285}} The formation of the corresponding carboxylic acid is a side reaction resulting from hydrolysis of the amide. When the alkyl group is an aliphatic chain (n typically 0 to 5), multiple reactions take place with the amide group always ending up at the terminal end. The net effect is thus migration of the carbonyl group to the end of the chain and oxidation.
File:Willgerodt general scheme.png
An example with modified reagents (sulfur, concentrated ammonium hydroxide and pyridine) is the conversion of acetophenone to 2-phenylacetamide and phenylacetic acidThe Willgerodt Reaction. II. A Study of Reaction Conditions with Acetophenone and Other KetonesDeLos F. DeTar and Marvin Carmack J. Am. Chem. Soc. 1946, 68(10), 2025 - 2029. ({{doi|10.1021/ja01214a047}})
Willgerodt–Kindler reaction
{{Reactionbox
| Name = Willgerodt–Kindler reaction
| Type = Rearrangement reaction
| NamedAfter = Conrad Willgerodt
Karl Kindler
| Section3 = {{Reactionbox Identifiers
| OrganicChemistryNamed = willgerodt-kindler-reaction
| RSC_ontology_id = 0000186
}}
}}
The related Willgerodt–Kindler reaction{{cite journal
| title = Studien über den Mechanismus chemischer Reaktionen. Erste Abhandlung. Reduktion von Amiden und Oxydation von Aminen
| author = Karl Kindler
| journal = Liebigs Annalen
| volume = 431
| issue = 1
| pages = 187–230
| year = 1923
| url =
| doi = 10.1002/jlac.19234310111}} takes place with elemental sulfur and an amine like morpholine. The initial product is a thioamide for example that of acetophenoneOrganic Syntheses, Coll. Vol. 9, p.99 (1998); Vol. 74, p.257 (1997). ([http://www.orgsynth.org/orgsyn/pdfs/CV9P0099.pdf Article]) which can again be hydrolyzed to the amide. The reaction is named after {{ill|Karl Kindler|de}}
File:Kindler mod Willgerodt.png
A possible reaction mechanism for the Kindler variation is depicted below:Name Reactions and Reagents in Organic Synthesis Bradford P. Mundy, Michael G. Ellerd, Frank G. Jr. Favaloro 2005 {{ISBN|0-471-22854-0}}
The first stage of the reaction is basic imine formation by the ketone group and the amine group of morpholine to give an enamine. This reacts as a nucleophile with electrophilic sulfur, similar to an Stork enamine alkylation reaction.{{verify source|reason=This is how the Stork reaction goes, but the previous wording "conjugate addition" instead suggests nucleophile into a conjuated electrophile|date=May 2023}} The actual rearrangement reaction takes place when the amine group attacks the thiocarbonyl in a nucleophilic addition temporarily forming an aziridine and the thioacetamide by tautomerization.