Prof. Dr. P. Walden. Optische Umkehrerscheinungen (Waldensche Umkehrung). “Die Wissenschaft.” Monographs from the natural sciences and technology. Edited by Prof. Dr. Eilhard Wiedemann, Friedr. Vieweg & Son, Braunschweig, 1919. 214 pp.

If, in an optically active, asymmetric carbon atom, one of the four radicals is replaced by a new radical, i.e. if a substitution is carried out, then stereochemistry teaches us that the replacing radical either takes the place of the former one, while the optical activity of the compound is preserved, or else racemization occurs (i.e. the new molecule no longer possesses rotatory power).

In 1896 P. Walden, by means of simple chemical substitution reactions under the action of inorganic reagents under ordinary

at temperature it proved possible to carry out the transition from one active body to its direct optical antipode without racemization and subsequent resolution.

The history of this discovery, which is of interest from the standpoint of the genesis of scientific creativity, is, in the author’s words, as follows:

In 1891–92 P. Walden, while working on the Handbuch der Stereochemie published jointly with C. A. Bischoff, and while collecting data concerning optical rotation, found a reference to Perkin [Journ. Chem. Soc. 53, 695, 701, 708, (1888)], who had obtained (by the action of phosphorus pentachloride on tartaric acid) chlorofumaric and chloromaleic acids and had prepared from them a dextrorotatory ethyl ester. Since the theory of van ’t Hoff concerning asymmetric carbon did not provide for optical activity in unsaturated compounds, while Le Bel admitted the possibility of activity in such derivatives, verification of Perkin’s data was of theoretical interest.

Walden’s experiments gave, both at temperatures above 100° and at 50–60°, inactive products, i.e. chlorofumaric acid together with dichlorosuccinic acid.

Walden became interested in the question why dichlorosuccinic acid, formed from active tartaric acid by simple substitution and containing two asymmetric carbon atoms, is formed only in an inactive form. Is the formation of an active halogen compound upon replacement of the hydroxyl of an asymmetric carbon by a halogen impossible in general, or possible only in exceptional cases?

Or is a fundamental question involved here, one touched upon by van ’t Hoff (in 1874) and by Hantzsch (1898): is the difference among the four groups attached to carbon sufficient for optical activity, or are other factors also influential in the appearance of the latter, for example, the nature of the radical?

Starting from levo malic acid, Walden, by the action of phosphorus pentachloride, obtained strongly dextrorotatory chlorosuccinic acid; replacing chlorine in this right-handed acid by hydroxyl, he obtained dextro malic acid, the optical antipode of the starting product; acting on the latter with phosphorus pentachloride, he obtained levo chlorosuccinic acid—the optical antipode of the above-mentioned acid, which upon replacement of the halogen by hydroxyl gives levo malic acid, i.e. the original starting product.

The author recalls his many conversations with van ’t Hoff about this “anomaly,” during which the latter acknowledged the insufficiency of his theory and repeatedly advised: “Propose something new yourselves.”

Emil Fischer assessed this optical cyclic process in the following way: “This discovery, after Pasteur’s fundamental investigations, was the most astonishing observation in the field of optically active substances.” It immediately revealed two factors: 1) the establishment of entirely new phenomena, whose practical significance consists in the fact that, alongside Pasteur’s classical method of resolution, they provide a new, independent method for the direct preparation of optical antipodes, and 2) that our prevailing conception of the structure of molecules (of the action and arrangement of valences) and of substitution phenomena in the molecule requires alteration and supplementation, since these new phenomena are in fundamental contradiction with the prevailing theory. This phenomenon, which immediately aroused interest, did not find an explanation. It is again beginning to attract attention.

the attention of chemists from 1907 onward, when E. Fischer, in connection with his classical synthesis of polypeptides, made use of this phenomenon to obtain halogenated fatty acids, which he needed for the synthesis of polypeptides. Since then a whole series of investigations has been carried out by outstanding scientists, and Academician P. I. Walden undertook the labor of collating all those cases that had been studied from the standpoint of “Walden inversion”—a labor that formed the content of the monograph Optische Umkehrerscheinungen, published by Vieweg.

The work of Academician P. I. Walden will not only be read with great interest by all who are interested in the progressive course of the development of scientific thought, but it will remain an indispensable reference book for all working in this field.

In a separate chapter all the theories proposed to explain this phenomenon are compared. In all, 17 theories have so far been proposed to explain this phenomenon, namely by the following scientists:

H. C. Armstrong (1896); Chr. Winther (1896); P. Walden (1898); R. Wegscheider (1907); Emil Fischer (1911); Le Bel (1911); A. Werner (1911); P. Pfeiffer (1911); E. Bulmann (1912); A. Noyes (1912); B. Holmberg (1913); J. Tadamer (1913); A. F. Holleman (1913); P. Pascal (1913); A. Weinberg (1914); J. Stark (1914)¹).

The author arrives at the following conclusions:

1. Before Walden’s discovery it was taken for granted, as a rule, that an optically active body and the derivative obtained from it have one and the same configuration (except in the case when racemization occurs in the preparation of the derivative). However, “Walden inversion” showed that such an à priori assumption cannot be made for those derivatives that are obtained by replacing some group situated at the asymmetric carbon atom.

2. On the basis of “Walden inversion” it follows that replacement of a group connected with the carbon atom may occur both with a change of configuration and without such a change, and that often, by almost quantitative simple substitution reactions, one can prepare the optical antipode of the initial substance.

3. The most recent investigations of active carbon may be summarized in the following proposition: with every substitution of an atom, the new molecule need not necessarily take the place of the substituent near the carbon atom, but may also take another position.

4. Thanks to this, a change of configuration by analogy with “Walden inversion” becomes possible also in the case of inactive bodies, and numerous substitution reactions hitherto regarded as abnormal receive a new illumination.

5. Thus “Walden inversion” has created new problems in the field of the experimental investigation of substitution phenomena in general and of such phenomena at the asymmetric carbon atom in particular. The question of the reaction mechanism in substitution even in the case of the simplest types requires further investigation.

6. The facts known so far seem to justify the view that the phenomenon of substitution is not simply a process of substitution, but

¹) Let us also note the paper by A. E. Uspensky in issue I of Communications on Scientific and Technical Works in the Republic (p. 16), “On the question of Walden inversion and on the possibility of having a criterion for judging the normality and abnormality of substitution reactions.”

consists of a series of processes that proceed in many phases, with the formation and decomposition of additive products; the study of additive and intermediate products therefore acquires special significance.

1. The question of the change in the magnitude and sign of the specific rotation during the substitution taking place at an active asymmetric carbon atom receives, thanks to the simultaneous possibility of a change in configuration, new illumination. The insufficiency of our present knowledge in the field of optical rotatory power is again revealed, since we cannot predict à priori whether the sign of rotation will be preserved during substitution or not, and whether a change in the direction of rotation will also be caused by a change in configuration.

At the same time, “Walden inversion” is also an extraordinarily rich source for speculative thought.

1. The conception of the four carbon valences as four forces directed immovably in space leads to an obvious contradiction. As a consequence of this,

2. the usual representation of the configuration of an asymmetric carbon molecule with the aid of spatial models of Kekulé, van ’t Hoff, etc., with these immobile valences, is admissible only conditionally—it represents a limiting case that exists approximately near absolute zero; and hence,

3. thanks to “Walden inversion,” a number of new conceptions have been introduced into science concerning the mechanism of substitution in general and, in particular, concerning “Walden inversion.”

The work of Academician P. I. Walden, comprising 214 pages, shows us that, despite the enormous work accomplished, even now, after two decades, we still do not possess a complete explanation of this phenomenon. We have many theories attempting to explain these phenomena, but we still do not have theories that could predict the result of reactions, and therefore “Walden inversion” still remains an open question, prompting new work and new investigations, since, as E. Fischer has already observed1, “only with a still greater increase in the observational material can one hope gradually to arrive at definite rules; so long as rotatory power is to serve as a guide, this still cannot be said.”

And quite similarly P. F. Frankland has also recently expressed himself2: “It is clear that a large series of experimental investigations must still be carried out before the numerous complex and extremely important results that originate from the phenomenon of Walden inversion will be fully elucidated.”

The work of Acad. P. I. Walden was begun before the war; for this reason the author has collected in an appendix all those works, investigations, theories, and attempts to explain this phenomenon that were given in the period 1914–1919.

M. A. Bloch.

1. Ann. d. Chemie, 381, 184 (1911). ↩

2. Journ. Chem. Soc. 103, 742 (1913). ↩