Walden Inversion

WALDEN INVERSION (Walden), a change in the configuration (see Stereochemistry) of an optically active substance occurring as a result of certain substitution reactions. Thus, when moist silver oxide acts on d-chlorosuccinic acid, an exchange of chlorine located at the asymmetric carbon atom (see Asymmetric carbon) for a hydroxyl group takes place, and d-malic acid is obtained. If, however, this acid is subjected to the action of phosphorus pentachloride, the hydroxyl is again replaced by chlorine, but instead of the expected starting material—d-chlorosuccinic acid—its optical antipode, l-acid, is formed. As a result of the same transformations from l-chlorosuccinic acid, the right-handed acid can be obtained. The successive performance of these reactions is expressed by the following scheme (circular optical process): PCl₅, d-chlorosuccinic acid → l-malic acid | AgOH PCl₅ AgOH d-malic acid → l-chlorosuccinic acid. A change in the sign of rotation of the polarization plane can also be achieved in the first substitution. Thus, for example, if optically active chlorosuccinic acid is treated not with moist silver oxide, but with a solution of caustic potassium or aqueous ammonia, malic acid is obtained, possessing reverse rotation: COOH COOH -C1 + KOH = HO CH₂COOH d-chlorosuccinic acid -H + KCl, CH₂COOH l-malic acid. These reactions, discovered in 1895 by Walden and therefore named the Walden inversion, were initially regarded as anomalous phenomena. Indeed, if one assumes that in substitution reactions the substituent takes the place of the departing atom or atomic grouping, the configuration of the molecule should be preserved. Soon, however, it was discovered that such phenomena occur very frequently and proceed so regularly that they constitute a definite rule. Emil Fischer, to whom organic chemistry owes an especially detailed study of the phenomena of the Walden inversion, gave them a quite plausible explanation. He believed that substitution reactions proceed in two stages. The first consists in the fact that as a result of the combination of reacting substances (e.g., chlorosuccinic acid and silver hydroxide or caustic potassium), an unstable molecular complex is formed, for example, [HOOC.CH(Cl).CH₂.COOH]₂Me, where Me = K or Ag. The second moment is the decomposition of this complex. In the case of optically active substances, the nature of the decomposition depends on the spatial and valence features of the atoms located at the asymmetric carbon atom. Thus, the incoming atom or group (hydroxyl) can take the place of the departing one (chlorine), and then a new substance is formed with the configuration of the original one (as in the case of the reaction with AgOH), or the decomposition is associated with a change in the arrangement of atoms at the asymmetric carbon atom, and the resulting substance possesses a new configuration (reaction of chlorosuccinic acid with KOH). In this case, a Walden inversion takes place. If, in the same reaction, both processes occur simultaneously (preservation and change in the initial arrangement of substituents), partially or completely racemized substances are obtained.

The Walden inversion is used in preparative chemistry; in particular, E. Fischer widely applied the Walden inversion to obtain optical isomers of amino acids, which made it possible to discover the specificity of the action of proteolytic enzymes depending on the optical configuration (structure) of the amino acids making up polypeptides (see). Lit.: Walden P., Optische Umkehrerscheinungen, Braunschweig, 1919.