Walden Inversion

What is Walden Inversion?

The phenomenon of inversion of configuration during a chemical reaction is known as Walden Inversion. Generally, Walden inversion is referred to as optical inversion. The inversion of configuration may or may not lead to the change in direction of rotation.

Walden’s inversion is the reversal of a chiral centre in a molecule in a chemical reaction. Since the molecule can form two enantiomers around the chiral centre, the Walden inversion transforms the structure of the molecule from one enantiomeric form to another.

Table of Contents

• Walden Inversion Reaction
• Walden Inversion Mechanism
• Walden Inversion Explanation
• Frequently Asked Questions

Walden Inversion Reaction

In 1896, Walden reported an inversion of optical rotation in the conversion of malic to chlorosulfonic acid by reaction with phosphorus pentachloride.

Walden inversion has been extensively studied with numerous reactants and optically active substances. Perhaps the most satisfactory explanation for the change in configuration was suggested by Werner in 1911 and is commonly known as the opposite face mechanism for the Walden inversion.

For example,

A Walden inversion occurs at a tetrahedral carbon atom during an SN2 reaction when the entry of the reagent and the departure of the leaving group are synchronous. The result is an inversion of configuration at the centre under attack.

Walden Inversion Mechanism

The stereochemical course of an SN2 reaction’s inversion of configuration is explained below.

Nearly 100 years ago, Paul Walden demonstrated that (+) malic acid could be converted to either (+) or (-) chlorosuccinic acid (2-chlorobutanedioic acid) with different reagents. Although the absolute configuration of each substance was not known at the time, it was clear that one of these processes occurred by inversion of configuration at the stereocenter and the other by retention.

A series of investigations definitely showed that the stereochemistry of a chiral substance is normally inverted during the course of an SN2 reaction.

To commend Walden for his work on the stereochemical course of substitution reactions, we sometimes refer to the stereochemistry of an SN2 reaction as Walden inversion.

The presence or absence of an asymmetric or a chiral carbon atom in a molecule is not only a criterion of dis-symmetry or chirality, and hence, enantiomerism, But it is certain that most of the molecules have chiral carbon atoms are optically active.

Walden’s inversion was to develop a scheme for deciding by which mechanism a particular reaction had proceeded or would proceed. Ingold and co-workers showed how to distinguish whether a substitution occurred by the synchronous or the sequential route by kinetic criteria. They then went on to explore the structural features and reaction conditions that promoted one or other of these mechanistic routes.

Basically, which mechanism occurs is decided by which transition state is lower in energy. This can be analysed in structural terms, concerning things such as the energetic cost of breaking the initial bond, the steric environment of the transition states and the potentially stabilising effects of the proposed solvent etc. Typically, in synthesis one wants to employ the stereospecific SN2 mechanism because it gives a single predictable product.

Walden Inversion Explanation

Stereochemistry refers to the arrangement of atoms in space, and most particularly to the “handedness” of chemical compounds. When a carbon atom is bound to four distinct groups, those groups are arranged about the carbon as if they were at the vertices of a tetrahedron with the carbon at its centre. As a result, there are two distinct such arrangements possible – these are non-superimposable mirror images of one another called enantiomers. Enantiomers have very similar chemical structures and so their chemical and physical behaviour is also very similar.

However, there are some chemical differences between them, and they have different optical activities, they rotate plane-polarised light in opposite directions. Walden has shown that it was possible by a series of reactions to convert an optically active substance into its enantiomer. Chemists at the time had assumed that substitution reactions of the sort Walden employed would proceed in a way that either kept the spatial arrangement the same or perhaps randomised the spatial arrangement.

Walden showed that at some point during his series of reactions, the groups around carbon had to systematically shift from one spatial arrangement to another. In the forty years after the discovery of Walden inversion, many additional inversions were discovered, however, not all substitution reactions on optically active starting products led to inversion, some resulted in the retention of configuration and others led to a mix of enantiomers products.