Barton and Hassel Share the Nobel Prize

Date December 10, 1969

Derek H. R. Barton and Odd Hassel studied the exact shape of molecules made from carbon atoms, facilitating greater understanding and predictions concerning these ubiquitous natural materials and introducing critical knowledge to the field of organic chemistry.

Locale Stockholm, Sweden

Key Figures

• Derek H. R. Barton (1918-1998), English organic chemist noted for his insightful views on the exact shape of complicated naturally occurring compounds, and cowinner of the 1969 Nobel Prize in Chemistry
• Odd Hassel (1897-1981), Norwegian physical chemist whose detailed studies of simple carbon-ring molecules laid the foundation for understanding molecules, and cowinner of the 1969 Nobel Prize in Chemistry
• William Henry Perkin (1838-1907), English organic chemist who attempted the earliest syntheses of cyclic compounds containing less than five carbon atoms
• Adolf von Baeyer (1835-1917), German organic chemist who was one of the giants of nineteenth century organic chemistry, and winner of the 1905 Nobel Prize in Chemistry

Summary of Event

Of all the varied arrangements of carbon atoms in the world of naturally occurring molecules, the ring has provided the greatest challenge and fascination for chemists. Organic chemists (whose chief concern is the way in which atoms are assembled in molecules and the reactions by which those molecules are formed and broken apart) and physical chemists attempted to understand the most basic and quantitative level of how molecules arrange and interact with one another.

One of the most famous German chemists of the late nineteenth century, Adolf von Baeyer, thought deeply about the geometry of such systems. He wondered why one finds five- and six-carbon rings in great abundance in nature and never any other size. Baeyer devised a clever explanation.

It was well established by 1885 that the carbon atoms in the most commonly found ring systems formed bonds having angles of about 109.5 degrees. If a three-carbon ring were to form, it would have to be a triangle; since Euclid’s time it had been known that such a geometric figure lay in a single plane and had interior angles of 60 degrees.

It seemed clear to Baeyer that such bonds would place a great strain on the carbon atoms forming them and would contribute greatly to the instability of the resulting molecule. By a similar argument, a four-carbon ring with bond angles of 90 degrees would also be highly strained and reactive. In contrast, five- and six-membered rings would have interior angles of 108 and 120 degrees, respectively, angles in good agreement with normal expectations for carbon-to-carbon bonds. At the same time, if the number of carbon atoms were to grow larger, so would the angles, straining the bonds, just as the smaller angles did.

Baeyer’s theory seemed to be a neat and reasonable explanation of then-current observations. In any experimental science, however, facts continue to be discovered and theories either must be able to include them in their scope or they must give way to new and more general explanations. Theories are meant to be guides for understanding and making predictions.

Early work in Baeyer’s laboratory seemed to support his speculations. William Henry Perkin undertook the synthesis of small ring compounds. (Synthesis for an organic chemist means making more complicated molecules from simpler ones. It is necessary that the exact structure of the starting material be known and that the chemical conversion be well understood.) Using a chain of carbon atoms, Perkin linked the first and last to form a ring, or cycle. He found that small rings could be prepared, but that they were markedly less stable than the common five- and six-membered examples. It was to be nearly a half century before the fundamental error in Baeyer’s theory would be widely appreciated.

Only five years after its publication, however, the most basic assumption of Baeyer’s theory was being questioned. As early as 1890, Ulrich Sachse noted that there was no fundamental reason why the six-carbon and larger rings must lie in a single plane and that the strain would be eliminated if a slight puckering was introduced. By building models of the six-membered cyclohexane ring, Sachse showed that two such forms should be strain-free: one shaped like a lawn chair and a second, which he called a bed or bathtub form. The state of theory and technique in organic chemistry at that time, however, doomed attempts to obtain any convincing evidence of the existence of the two forms, and Sachse’s idea was left for nearly thirty years.

In 1918, Ernst Mohr added the crucial thought that if two six-membered rings were linked together by sharing two common carbon atoms, two distinct forms could be expected. Most important, these could be interconverted only at a great cost of energy. By contrast, he suggested, the two forms of the simple six-carbon ring might be interconverted easily by the thermal energy available at room temperature. Then, in 1925, Walter Hückel succeeded in showing that two forms of the fused ring system did, in fact, exist.

These early and penetrating thoughts and experiments led directly to the revolutionary work of Derek H. R. Barton and Odd Hassel. They were awarded the 1969 Nobel Prize in Chemistry for demonstrating the unity and utility of these ideas. Hassel, a professor at the University of Oslo, studied the six-carbon ring directly by introducing one or more heavy atoms such as chlorine in place of hydrogen. In this way, Hassel was able to show, using X-ray and electron measurements, that the two forms suggested by Sachse actually existed. More important, Hassel showed that one form constitutes about 99 percent of the mixture because of the enhanced stability resulting from its greater energy efficiency. The two forms are interconverted about 1 million times a second at room temperature.

These important results were being obtained during the height of World War II, but because Hassel refused to publish his work in German journals, the Western scientific community was deprived of his most significant ideas and experimental findings for many years. His precise and fundamental studies of the simplest six-carbon rings were noteworthy.

Barton carried out his early work at the Imperial College (University of London) and at Harvard University. He studied Hassel’s work as it became available, and has acknowledged his debt to his colleague. Barton was honored for applying the detailed understanding of the six-membered ring to more complicated systems and their reactions.

It is especially important to appreciate the relationship between Hassel and Barton’s work. They did not work together in the usual sense; in fact, the war prevented all communication. In his important 1950 publication concerning the conformations of steroids, Barton acknowledges Hassel and cites many of Hassel’s articles. The example of how science is built with each advance dependent on earlier work could not be clearer.

The term conformation was not universally accepted and much less widely understood in 1950. Barton took pains in several of his earliest articles to define the word carefully and clearly. Chemists had accepted, since the classic work of Louis Pasteur, that, under appropriate circumstances, the same set of atoms could form more than one compound that differed only in the exact arrangement of those atoms in space. Now, they were being asked to accept that even a single molecular species could assume various spatial arrangements that differed significantly in energy.

Significance

It is not an overstatement to maintain that Hassel and Barton caused a revolution in the way organic chemistry is understood and practiced in the last half of the twentieth century. The results of their studies have, in the words of one eminent chemist, “lifted out of the chemical literature the flat formulas of the 1930’s and 1940’s and ’sic’ replaced them with the three-dimensional structures by which we view molecules.”

Except for numerical details, Hassel’s concept of the dynamic structure of six-carbon rings explains very well the chemistry of such systems. Furthermore, it laid the foundation for theoretical and experimental work carried out since 1943, that cyclohexane is the most studied and probably the best understood structure in modern organic chemistry. For example, the usual textbook representations fail to make clear that the pairs of hydrogen atoms connected to each of the six-carbon atoms fall into two distinct sets. Hassel showed convincingly that half occupy positions roughly perpendicular to the average plane of the carbon atoms, while the others deviate only slightly from that plane. Accepting this does not make its usefulness clear necessarily, but it was soon discovered that great energy differences are observed also when the attached atom(s) are something other than hydrogen. In this way, it is now possible to fix effectively a given ring in a particular spatial arrangement and study its chemistry in fine detail.

This breadth and depth of understanding is of fundamental importance because the six-carbon ring forms the basis of an almost incomprehensible array of compounds that occur in nature. Perhaps the most widely known is cholesterol. Cholesterol is known to make cell walls stronger and to increase their utility in keeping the materials and processes of life functioning in an orderly fashion. Cholesterol also provides the basic structure from which it is possible for the human body to synthesize the huge variety of steroids that serve as carriers of information in our chemical systems. Furthermore, this central molecule represents the starting material for the preparation of natural and human-made drugs so vital in the prevention and treatment of disease.

At the same time, it requires only the short step of changing an oxygen atom for a carbon atom to include an equally incalculable number of sugars and other carbohydrates in this picture of three-dimensional six-atom rings. In fact, this type of speculation was introduced by Jacob Böeseken, while Mohr and Hückel were making their contributions.

This new view of molecular structure, given extensive experimental validation by Hassel and developed so enthusiastically by Barton, has shown itself capable of explaining a large number of previously inexplicable experimental observations. As with any useful theory, conformational analysis is now called on to predict the outcome of new experiments. The success of these leaps into the future has made this approach one of the most powerful tools in the possession of modern chemists.

Bibliography

Andersen, Per, Otto Bastiansen, and Sven Furberg, eds. Selected Topics in Structure Chemistry: A Collection of Papers Dedicated to Professor Odd Hassel on His 70th Birthday, 17 May 1967. Oslo, Norway: Universitetsforlaget, 1967. This book contains a short sketch of Hassel and a study of his career titled “Forty-five Years of Achievement.” Both pieces are written by people who knew Hassel well. Includes a good photograph and an extensive bibliography of Hassel’s publications.

Barton, Derek H. R. “The Principles of Conformational Analysis.” In Les Prix Nobel en 1969. Stockholm, Sweden: Imprimerie Royal, 1970. This article is very technical, but also contains carefully presented definitions and historical background. Accompanied by excellent references, photograph and career summary, and a most important introductory speech.

Eliel, Ernest L. “Nobel Laureates in Economics, Chemistry, and Physics.” Science 166 (November 7, 1969): 718-720. This article offers genuine and readable insight on very difficult concepts, coupled with excellent personal appreciations.

Finley, K. Thomas. “The Synthesis of Carbocyclic Compounds: A Historical Survey.” Journal of Chemical Education 42 (October, 1965): 536-540. Places emphasis on the ring strain theory of Baeyer and the work and personality of the scientists who brought it to its modern form. Offers good background for understanding conformations.

Wade, L. G., Jr. Organic Chemistry. 6th ed. Upper Saddle River, N.J.: Pearson Prentice Hall, 2006. Considered a classic work in outlining organic chemistry in a clear, understandable way. Emphasizes problem-solving. A massive, best-selling text at more than thirteen hundred valuable pages.

Wasson, Tyler, ed. Nobel Prize Winners. New York: H. W. Wilson, 1987. This book offers biographical sketches of Nobel Prize winners, placing emphasis on their work. Includes excellent photographs, but only limited references.