:Walden inversion

{{short description|Chemical reaction mechanism}}

Image:Walden-inversion-3D-balls.pngs, of the three steps in an S_N2 reaction. The nucleophile is green, the leaving group is red and the three substituents are orange.]]

Image:SN2-Walden-before-and-after-horizontal-3D-balls.png

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 S_N2 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 S_N2 reaction gives rise to a product whose configuration is opposite to the reactant. Therefore, during S_N2 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

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.{{cite journal | last=Buchanan | first=J. Grant | last2=Diggle | first2=Richard A. | last3=Ruggiero | first3=Giuseppe D. | last4=Williams | first4=Ian H. | title=The Walden cycle revisited: a computational study of competitive ring closure to α- and β-lactones | journal=Chemical Communications | publisher=Royal Society of Chemistry (RSC) | issue=10 | year=2006 | issn=1359-7345 | doi=10.1039/b517461a | page=1106}}