Walden inversion is the inversion of a
stereogenic center in a
chiral molecule in a
chemical reaction. Since a molecule can form two
enantiomer
In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
s 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
Paul Walden ( lv, Pauls Valdens; russian: Павел Иванович Вальден; german: Paul von Walden; 26 July 1863 – 22 January 1957) was a Russian, Latvian and German chemist known for his work in stereochemistry and history of che ...
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 PCl
5 returned the cycle to its starting point.
:
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
In biology and other experimental sciences, an ''in silico'' experiment is one performed on computer or via computer simulation. The phrase is pseudo-Latin for 'in silicon' (correct la, in silicio), referring to silicon in computer chips. It ...
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.
See also
* Another demonstration of the Walden cycle in the
Brook rearrangement.
References
{{Reflist
Substitution reactions
Reaction mechanisms