Otto Paul Hermann Diels

German chemist

• Born: January 23, 1876
• Birthplace: Hamburg, Germany
• Died: March 7, 1954
• Place of death: Kiel, West Germany

Diels made two fundamental contributions to classical organic chemistry: the selenium dehydrogenation and the diene reaction. The selenium reaction made it possible to establish the structure of a large number of important natural materials, notably the steroids. The diene reaction is unique in its variety, durability, and quality. Diels was awarded the Nobel Prize in Chemistry with Kurt Alder in 1950.

Early Life

Born into an intellectual family, Otto Paul Hermann Diels (deels) was the second of three sons. Little is known about his mother and two sisters, but his father, Hermann, was appointed professor of classical philology at the University of Berlin, only two years after Otto’s birth. It is not surprising that education was of prime importance and that the sons were inspired to follow university careers. The eldest son, Ludwig, became a professor of botany at Berlin, and the youngest, Paul, a Slavic philologist at Breslau. In their school days, Otto and Ludwig carried out chemical experiments together. When Diels was only thirteen at the Joachimsthalches gymnasium, he was taught by the talented Karl Schellbach, and his father gave him one of the standard chemical textbooks of the day.

Life’s Work

Diels represents the highest ideal of the classical organic chemist. He recognized fundamental problems and was unafraid to attempt their solution. When a particularly useful observation was made, he quickly recognized it and tenaciously pursued its development. During the first decade of his career as a chemist, Diels was under the direct influence of the 1902 winner of the Nobel Prize in Chemistry, Emil Fischer, whom he greatly admired. This training period took place at the University of Berlin, where Diels obtained his doctorate, magna cum laude, in 1899. Another Nobel laureate, Richard Willstätter, described Fischer as the last example of a chemist who employed simple experiments and direct observation. It can be argued that his student, Diels, brilliantly continued that tradition with a genius for discovering and exploiting synthetic methods of fundamental significance. It is a rare chemist who is able to produce a technique or reaction that becomes universally accepted as the method of choice; Diels found two.

In his earliest independent studies, Diels became interested in the extremely complex structure of cholesterol, the most widely known of the steroids, which has been an object of active research years after its structure had been firmly established. In 1900, few details of cholesterol’s structure were known in spite of more than a century of effort. A proposal had been made for the four-carbon atom rings known to be present; Diels, however, believing strongly that the structure was not consistent with the evidence, sought to find a method for determining the correct ring sequence.

Cholesterol is known as a hydroaromatic, which is to say that the three rings consisting of six carbon atoms each contain the element hydrogen in an approximate 2-to-1 ratio with carbon. Diels reasoned that if cholesterol were converted to an aromatic compound it would be easier to study and its ring structure more easily deduced. An organic chemist does not think of aromatic compounds for their odor but rather in electronic terms. Their structure is characterized by a much lower hydrogen/carbon ratio of around one to one. One of the methods for removing hydrogen from a molecule involves heating it with sulfur, but cholesterol failed to respond to this treatment. Diels tried a little-known relative of sulfur, the element selenium. It soon became apparent that his insight had uncovered a milder and more general method that has been universally employed. The aromatic product was so important in establishing the structure of such natural products as sex hormones, D-vitamins, adrenal-cortex hormones, toad venom, and bile pigments that it was often referred to as the Diels hydrocarbon.

Cholesterol is not unusual in having several six-atom rings in its structure. While a wide variety of ring sizes are known to occur in nature, it is the six-membered ring that is by far the most common. Unlike the rings of cholesterol, where all rings are all-carbon atoms, many natural molecules contain other atoms such as oxygen or nitrogen. In spite of the frequency with which they occur, rings of any size are rather difficult to form except in certain special instances. In the mid-1920’s, Diels and his students showed that two compounds containing particular atomic and electronic arrangements form six-atom rings with great ease. The essential electronic demands of the reaction are that both molecules have atoms held together by more than one pair of electrons, that is, double or triple bonds. Furthermore, one member of the pair, the diene, must have two such arrangements separated by a single bond. The name diene is almost always used whatever the complexity of the actual molecule under consideration; originally, the reaction was referred to as the diene synthesis. Later it was referred to as the Diels-Alder reaction for Diels and his student and codiscoverer, Kurt Alder. Originally, the second component was called a “philodiene,” but the variant “dienophile” has since been employed; both names suggest the great ease with which these two unite. Not all the atoms need be carbon, as represented in Diels’s original example in which the dienophile contained a nitrogen-nitrogen double bond. This is an addition reaction, since the product is simply the sum of the original two reacting molecules. No atoms are lost to by-products, nor are any added on from other reagents. The chemistry involved is simply the rearrangement of shared pairs of electrons.

In large measure, it is the extremely mild conditions demanded by the reaction that make it so useful in preparing the fragile molecules of nature. A second aspect of this reaction leading to its rapid and general inclusion as the standard method of synthesis for six-membered rings is the wide range of application it has had. The third characteristic of Diels-Alder chemistry of vital importance to the synthetic and to the theoretical chemist is the high degree of stereochemical specificity obtained from its use. In cases where more than one arrangement of the product atoms is possible, the probability of being able to predict the one that will actually be obtained is quite high.

These highly desirable features have made the Diels-Alder reaction a key step in the synthesis of a large number and variety of complex natural products, for example, the steroid cortisone. Its first total synthesis belongs to Nobel laureate Robert Woodward of Harvard University and was followed closely by that of Lewis H. Sarett. Both syntheses involved Diels-Alder reactions as key steps.

Diels continued his collaboration with Alder even after the latter left Kiel. Their work centered on understanding the nature of the cyclization process and placed a special emphasis on its stereochemistry. This area of organic chemistry examines the exact three-dimensional arrangement of the atoms in a molecule and is of great importance since in the absence of symmetry a small change can produce a totally different compound.

Furthermore, naturally occurring compounds almost always possess only one of the possible arrangements and fail to be useful in the alternative form. Alder was able to show that the cyclization is very specific and in general gives only one of the stereochemical possibilities.

During World War II, much in Diels’s life was destroyed, including two of his sons and the university together with its laboratories and library. After requesting retirement in 1944, he submitted to the needs of his colleagues and returned to active service to rebuild the institute where he had worked. After his permanent retirement in 1948, he completed editing the fifteenth edition of his highly regarded textbook, Einführung in die organische Chemie (introduction to organic chemistry), first published in 1907. In 1950, Diels and Alder were awarded the Nobel Prize in Chemistry for their work in diene synthesis. Diels was too ill to deliver his lecture in Stockholm; he died four years later, on March 7, 1954.

Significance

Diels was one of the last of the great pure organic chemists. Synthesis was its own reward; the sheer joy of making new compounds by imaginative methods seems to have been his motivation. He had no interest in the theory of chemical reactions or their use in biochemical systems. By today’s standards, his approach to science appears quaint, but however old-fashioned it might be, his method has been used as an important synthetic tool. His contribution was a great one.

Diels’s discovery has been at the center of speculation and experiment in the modern world’s attempts to understand the deepest secrets of molecular interactions. The number of first-rate scientists who have contributed to an appreciation of Diels-Alder chemistry is a fitting tribute. Diels might not have understood the interest of modern scientists in his reaction, but his love of students would have led him to be proud of the accomplishments that his reaction made possible.

Bibliography

Alder, Kurt. “Diene Synthesis and Related Reaction Types.” In Les Prix Nobel en 1950. Stockholm: Imprimerie Royale, 1950. A full review of the Diels-Alder reaction from the earliest days to the most current problems then being investigated. Alder places special emphasis on the theory and stereochemistry of the reaction. Of necessity, the material is fairly technical and presented at a rapid pace, but this is a good introduction to the chemistry and its meaning.

Diels, Otto Paul Hermann. “Description and Importance of the Aromatic Basic Skeleton of the Steroids.” In Les Prix Nobel en 1950. Stockholm: Imprimerie Royale, 1950. A modest and revealing description of Diels’s several contributions to the final solution of the complicated structure of cholesterol. He gives full credit to the contributions made by his colleagues at other universities. The paper is preceded by the important presentation speech by Arne Fredga of the Nobel committee. These few pages give a remarkably clear and nontechnical description of the diene synthesis. Following Diels’s paper is a brief but very useful biographical sketch.

Finley, K. Thomas. “The Synthesis of Carbocyclic Compounds: A Historical Survey.” Journal of Chemical Education 42 (October, 1965): 536-540. While relatively little space is given to the Diels-Alder reaction, it is noted as one of the most important accomplishments in synthetic chemistry. Most useful for placing Diels’s contribution in perspective with the entire field of ring-forming chemistry.

Karty, Joel. The Nuts and Bolts of Organic Chemistry: A Student’s Guide to Success. San Francisco, Calif.: Benjamin Cummings, 2006. An excellent, easy-to-follow and understand introduction to organic chemistry, written especially for students. Focuses on comprehension, not memorization. Recommended.

Mehta, Goverdhan. “Molecular Design of Compounds Via Intermolecular Diels-Alder Reactions.” Journal of Chemical Education 53 (September, 1976): 551-553. In spite of its title, this article explores a number of extremely interesting intramolecular Diels-Alder reactions. Quite technical but well worth the effort.

Willcox, T. J. “Otto Diels, 1876-1954.” Education in Chemistry 13, no. 1 (1976): 7-9. Written for the centennial of Diels’s birth, this brief article is one of the very few biographical works in the English language with the exception of dictionaries of scientists. Very important for insights into Diels’s early life and his limited nonchemical interests, which are otherwise available only in German. Also covers his scientific contributions in good detail; appropriate for general readers.