Walden inversion

---

title: "Walden inversion" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public tags: ["substitution-reactions", "reaction-mechanisms"] description: "Chemical reaction mechanism" topic_path: "general/substitution-reactions" source: "https://en.wikipedia.org/wiki/Walden_inversion" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Chemical reaction mechanism ::

::figure[src="https://upload.wikimedia.org/wikipedia/commons/b/bb/Walden-inversion-3D-balls.png" caption="S_N2 reaction]]. The nucleophile is green, the leaving group is red and the three substituents are orange."] ::

::figure[src="https://upload.wikimedia.org/wikipedia/commons/4/46/SN2-Walden-before-and-after-horizontal-3D-balls.png" caption="The S_N2 reaction causes inversion of stereochemical configuration, known as Walden inversion."] ::

Walden inversion is the inversion of a stereogenic center in a chiral molecule in a chemical reaction. Since a molecule can form two enantiomers around a stereogenic center, the Walden inversion converts the configuration of the molecule from one enantiomeric form to the other. For example, in an SN2 reaction, Walden inversion occurs at a tetrahedral carbon atom. It can be visualized by imagining an umbrella turned inside-out in a gale. In the Walden inversion, the backside attack by the nucleophile in an SN2 reaction gives rise to a product whose configuration is opposite to the reactant. Therefore, during SN2 reaction, 100% inversion of product takes place. This is known as Walden inversion.

It was first observed by chemist Paul Walden in 1896. He was able to convert one enantiomer of a chemical compound into the other enantiomer and back again in a so-called Walden cycle which went like this: (+)-chlorosuccinic acid (1 in the illustration) was converted to (+)-malic acid 2 by action of silver oxide in water with retention of configuration. In the next step the hydroxyl group was replaced by chlorine to the other isomer of chlorosuccinic acid 3 by reaction with phosphorus pentachloride. A reaction with silver oxide yielded (−)-malic acid 4 and finally a reaction with PCl5 returned the cycle to its starting point.{{cite journal | title = Ueber die gegenseitige Umwandlung optischer Antipoden | author = P. Walden | journal = Berichte der deutschen chemischen Gesellschaft | volume = 29 | issue = 1 | pages = 133–138 | year = 1896 | url = https://zenodo.org/record/1425826 | doi = 10.1002/cber.18960290127 }}

:[[File:Walden inversion.png|alt=Walden cycle|center|500x500px]]

In this reaction, the silver oxide in the first step acts as a hydroxide donor while the silver ion plays no role in the reaction. The intermediates are the carboxyl dianion A which gives an intramolecular nucleophilic substitution by the β-carboxylate anion to produce a four-membered β-lactone ring B. The α-carboxyl group is also reactive but in silico data suggests that the transition state for the formation of the three-membered α-lactone is very high. A hydroxyde ion ring-opens the lactone to form the alcohol C and the net effect of two counts of inversion is retention of configuration.

References

References

1. (2006). "The Walden cycle revisited: a computational study of competitive ring closure to α- and β-lactones". Royal Society of Chemistry (RSC).

::callout[type=info title="Wikipedia Source"] This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page. ::