The willgerodt‐kindler reactions. 7. The mechanisms

Abstract

The mechanisms involved in various stages of the Kindler Reaction are discussed, with particular attention especially to its most unusual feature: the movement of a carbonyl group from methylene carbon to methylene carbon in an unbranched alkyl chain, or around a cycloalkyl ring. The first step is the reversible formation of an enamine, which is attacked by a catalyst generated from sulfur and the amine solvent to form a highly reactive intermediate with a sulfur‐containing heterocyclic ring. The natures of the catalytically active species and the reactive intermediates are proposed. Other steps involved in the Kindler Reaction are also discussed, as is the relationship of the Willgerodt Reaction to the Kindler Reaction.

Interesting Behavior of Acetone under the Willgerodt-Kindler Reaction Conditions

“…As shown in Scheme 3, Carmack has proposed a possible mechanism for the formation of simple thioamides, such as 2 [20]. Although the formation 2 is completely in agreement with this proposition, it is probably unreasonable to expect a single mechanism for this reaction to form all products 1 -4.…”

Insight into the Willgerodt-Kindler Reaction of ω-Haloacetophenone Derivatives: Mechanistic Implication

“…The reaction proceeded to completion at room temperature in 24 h. Using excess sulfur does not create a problem with regard to the purity of the final product as far as the amine is also used in sufficient excess (here 3 equivalents) and therefore these side-products are easily removed during the work-up. The reactive intermediates involved in the WK reaction are indeed in great part polar water-soluble nitrogen-sulfur species formed by ring opening of octasulfur by the nucleophilic attack of the amine [23]. DMF (at room temperature) was found greatly beneficial as reaction in refluxing diethyl ether (∼35 ∘ C) required a rather long reaction time, typically 36 h.…”

Synthesis of 1,n-Acyloxy Thioamides by the Willgerodt-Kindler Reaction: Chemoselectivity of 1,3-Ketoesters over 1,3-Diketones

“…A mechanistic study led to the chemoselective thioamidation of 1,3-ketoesters in the presence of 1,3-diketones. This is a new finding for the WK reaction which can be helpful for elucidating its reaction pathway that still remains obscure [13,18].…”

“…The excellent work by Carmack [18] has proved that an enamine plays a critical role as an intermediate in the migration of a carbonyl group back and forth along a chain of methylene units via a facile isomerization induced by catalytic action of a dithio-bisamine generated from sulfur and amine (Scheme 3). In other words, the enamine is attacked by a dithio-bisamine to form a highly reactive three-membered ring heterocyclic sulfur intermediate which facilitates the elimination-readdition of the amines reversibly along Scheme 3.…”