Cyclic compounds

Type of physical science: Chemistry

Field of study: Chemical compounds

Carbon has the capacity to form complex molecules involving many atoms of that single element. Among the most widely studied forms of organic, or carbon, compounds are the cyclic, or ring, structures. Many are found in nature, and their investigation has proved to be a sensitive method for obtaining information concerning structure and reactivity.

Overview

Of all the elements in the periodic chart, carbon has the greatest ability to form more than a few bonds between atoms of its own kind. Oxygen is found mostly as diatomic molecules (O₂) and occasionally as ozone (O₃), but many thousands of carbon compounds with five, ten, thirty, and hundreds of carbon atoms linked together by shared electron pairs have been found.

Carbon also has the ability to form strong bonds with a variety of other elements. In the most common cases, involving carbon, oxygen, or nitrogen, carbon often shares more than one pair of electrons.

With this diversity, it is not surprising to find that sequences of carbon atoms, alone or mixed with oxygen, nitrogen, and other elements, form cyclic structures by uniting the ends of a chain of atoms. What is astonishing is the frequency with which such molecules occur in nature and the fascination they have provided for chemists since the early years of the nineteenth century.

In the early 1830's, shortly after Friedrich Wohler had shown that the synthesis of organic compounds is possible, he and his friend Justus von Liebig began the study of the carbon compound that is found in the oil of bitter almonds. They demonstrated that a substantial portion of the carbon structure of this compound remains intact as the molecule is changed from one chemical to another. It was to be forty years before a structure was proposed that could successfully account for the marvelous properties of this group of atoms.

In 1865, August Kekule proposed that the six carbon atoms form a ring. Most of benzene's chemical behavior is now attributed to the presence of six closely associated electrons, but the ring makes it possible. Since the earliest known structures of this type had fragrant odors, benzene-based compounds are still referred to as aromatics.

During the mid-nineteenth century, chemists learned that the carbon compounds related to oils also contain rings. These alicyclic compounds use their electrons to bond with hydrogen atoms and are often referred to as saturated, since they have about twice as many hydrogens as the aromatic series.

In the later nineteenth century, it had become apparent that rings of six carbon atoms were the most common structural arrangement in the natural world. Some examples of five-carbon-atom rings were also known in the alicyclic series, but there were no recognized examples of any other ring sizes.

Such a remarkable observation offered an irresistible challenge to chemists who love to propose explanations. The great experimentalist Adolf von Baeyer suggested why there are only five- and six-atom rings, never three-, four-, seven-, or eight-. Observing Euclid's demand for 60-degree interior angles in an equilateral triangle and carbon's normal bond angle of about 109 degrees, he concluded that the three-carbon ring would be highly strained and therefore unstable.

If one extends the ring strain theory to the square of a four-carbon ring, the deviation is less but still substantial. The regular pentagon and hexagon angles of 108 degrees and 120 degrees, respectively, provide the minimum strain and account for their widespread occurrence and relative ease of synthesis. Exactly why the six-atom ring was more common than the far more strain-free five-atom ring was never made clear. Larger rings contain progressively greater amounts of strain, resulting in the normal bond angles being spread wider and becoming more unstable and less likely.

The theory, like the original observation, presented a challenge that could hardly be ignored, and in a few years, the basic reason for its existence had been destroyed. Three- and four-carbon rings were prepared in a variety of ways and, in due course, were found in natural compounds. A basic function of any scientific theory is to stimulate efforts to prove that it is untrue and unnecessary.

Proving the existence of and synthesizing larger rings took longer, but it was only five years before chemists were questioning the basic assumption that the rings are flat. Ulrich Sachse found that six-carbon rings in a puckered arrangement are without strain. Molecular models show that the idea is correct, but they also show two different forms. These two isomeric forms, however, had not been found, and the idea was nearly forgotten.

Isomers are different compounds that share the same composition, or number and kind of atoms, but have structures that are not identical. Nearly thirty years later, E. Mohr suggested that the failure to find the expected structural forms might simply result from their being easily interconverted. He showed that when two six-carbon-atom rings are joined by sharing two adjacent atoms, they exist in two forms that could be interconverted only with great difficulty.

Seven years later, W. Huckel isolated these two different molecules.

With the assurance that larger rings were reasonable synthetic goals, chemists became more adventurous in their search for methods by which to make them. Rings larger than six atoms proved perfectly stable once prepared, but the task of actually making them in the laboratory represented a worthy challenge for the large number of first-rate chemists who developed new techniques and apparatuses for the synthesis of cyclic compounds.

Two or more rings each sharing a common carbon-carbon bond or side are found in many natural materials and are referred to as fused rings. It is also possible for two rings to share a single carbon atom. Such spirocyclic systems are well known and exhibit fascinating chemistry. More than one ring can exist in a molecule held together by a chain of carbon atoms.

Alternatively, rings can interrupt the carbon chain, that is, actually be a part of the chain. Both the alicyclic and the aromatic series are well represented in all these categories.

Rings can also be constructed in such a manner as to have a larger ring divided into two or more smaller rings. Such bi- or tricyclic molecules are common in nature and have provided one of our most difficult technical and intellectual problems.

No discussion of cyclic compounds could be considered complete without mention of the bizarre outer limits of the chemists' imagination. Suppose you were making large-ring compounds from long-carbon-chain molecules by having one end react with the other. This process is not simple--it would be easier for the ends of two different molecules to link up--but it can be done. It could happen that an open chain is threaded through a ring when reaction takes place, in which case two rings would be connected like two links in a chain. Should this be considered one molecule or two?

Still another variation in the construction of cyclic molecules is found in the realization that not all the atoms in a ring need to be the element carbon. Nitrogen and oxygen are frequently found as components of cyclic compounds. Sulfur and phosphorus are also often incorporated in cyclic systems. In principle, any atom that forms more than one bond with carbon can be a part of a ring compound, and it is likely that at least one example has been prepared and the results published in the chemical literature.

Neither is it necessary to limit the number of noncarbon atoms in a ring. Many examples are known in which two, three, four, or more nitrogen atoms are present in a single ring. In the extreme, it is not necessary that any carbon be present; such examples do exist. It in no way lessens the truth of the assertion that carbon is unique in its ability to form many bonds with other carbon atoms to learn that a common form of sulfur is a ring of eight sulfur atoms.

Consider for a moment that the common forms of pure carbon, the diamond and graphite, are made of carbon atoms bonded to four other carbon atoms. Thus, by definition, both these forms of the element consist solely of rings of pure carbon.

Applications

The size of carbocycles has had unexpected consequences. One of the most exciting developments in chemistry of the mid-twentieth century was the discovery that aromatic chemistry was not restricted to the six-atom ring. Some of these non-benzenoid aromatics have an extra or missing electron.

In 1960, E. Wasserman studied the problem of rings formed in the presence of other rings by examining chains of thirty-four carbon atoms. He obtains solid experimental evidence that the catenanes not only are conceivable but are actually present in such a synthesis. In 1989, Nobel laureate Donald J. Cram prepared a cyclic compound that completely surrounds a volume of space and is large enough to enclose completely a second molecule. Both these structures raise the question, Is this one molecule or two?

Cyclic compounds are of broader interest than to the research scientist; an example of a simple cyclic molecule that is widely used is epoxy glue. To the chemist, an epoxide is a ring containing two carbon and one oxygen atoms. When heat or another chemical, called an initiator, is added, the highly strained ring opens and forms strong bonds with other molecules.

The most common of all organic molecules is the simple sugar glucose, so familiar in hospitals. All the varied starches that humans depend upon for good nutrition are made of polymers, long chains of glucose molecules. The glucose is present as six-membered rings that include one oxygen atom. The equally varied natural building material cellulose is also a polymer of glucose rings. There are usually more than one thousand glucose units in each molecule.

Glucose also makes up half of sucrose, common table sugar, along with fructose, or fruit sugar. Fructose and glucose are similar in structure; in fact, they are isomers. The five-member fructose ring constitutes their most distinctive difference.

In the 1920's, the Swiss chemist Leopold Ruzicka determined that the prized odors of the Asiatic musk deer and the African civet cat were produced by cyclic carbon compounds containing fifteen and seventeen atoms, respectively. This work brought him the Nobel Prize in Chemistry in 1939.

The task of preparing these rare, exotic rings synthetically would be of great benefit to the Swiss economy, not to mention the animals killed for microscopic drops of their scent. In the 1930's, however, there was very little prospect of accomplishing such a feat. Swiss industry and ingenuity are well represented by Max Stoll and Vladimir Prelog, who found methods useful for the synthesis of both the commercially important large rings and the elusive medium rings of seven to ten carbon atoms. These compounds have contributed to many important studies because of their special geometric restrictions and possibilities. Prelog's 1975 Nobel Prize in Chemistry was for his work in stereochemistry, or the study of the exact arrangement of atoms in space. Cyclic molecules are found in many of his most important works.

In spite of the now well-established presence and importance of the small and large cyclic molecules in nature and industry, it is still the five- and six-atom systems that continue to demand scientists' attention. Few molecules have received as much press, both good and bad, as has cholesterol. A proper diet is required to ensure that this molecule constructs cell walls and does not clog the blood vessels. Nature could hardly have produced a more elegant molecular structure than cholesterol, with its four rings, three of six carbons and one of five. Each of these subunits is fused to its neighbors in such an exact stereochemical relationship that, of the 256 possible arrangements, only one is in every respect cholesterol.

Otto Diels, a German chemist, made important contributions to the current understanding of the structure of cholesterol before he and Kurt Alder won the 1950 Nobel Prize in Chemistry. That honor came not for work on cholesterol but for the discovery and development of a brilliant method for the synthesis of six-atom rings. This technique, now known as the Diels-Alder reaction, is certainly the most widely investigated and utilized method in all of organic chemistry. Its popularity is attributable in part to the frequency of six-carbon ring systems, but the reaction itself has provided insight into the working of chemical systems beyond what its discoverers could have imagined.

The steroids comprise a vast array of compounds found in nature and an even larger number of synthetic creations. They play so many and such varied roles in the maintenance of good health and treatment of disease that lavish amounts of research have been expended on their synthesis. Many steroids possess the basic ring structure of cholesterol; others have one aromatic ring or other distinctive structural features.

The element nitrogen is also found in many cyclic natural products. It was recognized early in the study of organic chemistry that many plants with pharmaceutical properties contained basic nitrogen compounds, which we call alkaloids. Such common substances as the painkiller morphine, the malaria drug quinine, the tranquilizer reserpine, the stimulants caffeine and nicotine, and drugs like cocaine and LSD, all contain at least one ring involving a nitrogen atom. Few molecules are more central to life than hemoglobin and chlorophyll. In both cases, a huge ring containing four five-membered rings, each with a nitrogen atom, is involved. The beauty of these complex structures can only be appreciated by viewing their three-dimensional models and reading the real-life mystery stories of the long, complex trails leading to their synthesis.

Cyclic compounds containing nitrogen and oxygen or nitrogen and sulfur are often present. For example, morphine contains an oxygen atom in one of its five rings. Penicillin has two rings, one of which contains both a nitrogen and a sulfur atom. A similar cyclic system is found in vitamin B1, in which a separate aromatic ring contains two nitrogen atoms.

One of the most revolutionary scientific events of the twentieth century was the discovery of the structure of deoxyribonucleic acid (DNA) and its role in transmitting genetic information. The 1962 Nobel Prize in Physiology or Medicine was awarded to James Watson, Francis Crick, and Maurice Wilkins for their successful efforts to construct a suitable model of DNA. Their proposal involved two separate chains of nucleic acids held together by bonds between hydrogen atoms on one chain and electron pairs on the other. The key structural feature in this picture is the existence of pairs of nitrogen bases, which hold the atoms and electrons at exactly the right distances and locations for the most effective bonding. These bases are matched pairs, consisting of single rings containing two nitrogen atoms and two ring compounds containing four nitrogen atoms.

Context

One measure of the importance of the ring compounds might be the number of Nobel Prizes that have been directly connected with their synthesis, discovery, or utilization. This figure suggests the number of first-rate minds their study has attracted during the twentieth century.

One should also not forget the large number of fine scientists who worked on cyclic compounds long before Alfred Nobel established his premier award. Only a few have been mentioned here.

The substances themselves show a variety of elegance, both of structure and application, from nature's deadly poison strychnine to the life-saving human creations the sulfa drugs. Everywhere, cyclic molecules are abundant. Everything we learn about the chemical nature of ourselves and our world teaches that the exact shape of molecules is of vital importance for their proper functioning.

Isomers can be studied as individual compounds and conformers or as different forms interconverting so rapidly that they appear to be a single substance. This distinction can be made for all organic compounds, not merely the carbocyclic molecules.

With World War II raging all around him, the Norwegian chemist Odd Hassel studied the exact structure of the six-carbon ring, cyclohexane. Derek Barton, in England and America, applied these findings to complex ring systems such as the steroids. Chemists would never again look at molecules as flat drawings in textbooks, but as live, three-dimensional structures.

Principal terms

ATOM: the smallest particle of an element that retains all the chemical and physical attributes of the substance

BOND: one or more pairs of electrons that are responsible for holding atoms together; in carbon compounds, these are shared pairs, or covalent bonds

COMPOUND: a pure chemical made up of two or more elements bonded to one another

CONFORMATION: a particular arrangement of a molecule in space, which can be converted to another arrangement without a great cost in energy

COVALENCE: the number of chemical bonds, or pairs of electrons, shared by an atom with other atoms in making a molecule

CYCLIC: as used here, a molecule in which at least some part of the structure consists of a sequence with the last atom bonded to the first

FORMULA: the chemical composition of a compound; used to designate both the number and kinds of atoms and their structure

HYDROGEN BOND: an attraction, less powerful than a covalent bond, between a hydrogen atom attached to an atom like nitrogen, oxygen, or sulfur, and an unshared pair of electrons on some other atom

MOLECULE: a collection of atoms bonded together to form a structure that exists as a discrete entity and possesses at least enough stability to be detected

STRUCTURE: the exact arrangement of atoms in a molecule; especially, their spatial distribution

Bibliography

Benfey, O. Theodor. FROM VITAL FORCE TO STRUCTURAL FORMULAS. Boston: Houghton Mifflin, 1964. The early, frustrating years of organic chemistry are described by selected, translated quotations from its founders. Studies of benzene and the oil of bitter almonds are discussed. Historical perspective is provided in the text and in brief biographical sketches. Suggestions for further reading are included.

Finley, K. Thomas. "Ladenburg and the Cup of Hemlock." CHEMISTRY 41 (January, 1968): 18-21. Story of the molecule used to take Socrates' life. The first alkaloid to be synthesized contains a single ring of six atoms, including one nitrogen. Especially important for its discussion of stereochemistry.

Finley, K. Thomas. "The Synthesis of Carbocyclic Compounds: A Historical Survey." JOURNAL OF CHEMICAL EDUCATION 42 (October, 1965): 536-540. The people who began the study of cyclic chemistry and those who continued to investigate these fascinating structures. Emphasizes the alicyclic compounds and the competitive nature of research.

Finley, K. Thomas, and James Wilson, Jr. FUNDAMENTAL ORGANIC CHEMISTRY. Englewood Cliffs, N.J.: Prentice-Hall, 1970. A textbook giving a brief view of organic chemistry and making few assumptions of previous knowledge. More treatment of cyclic compounds than is typical. Good historical and biographical perspectives. Additional reading lists. Contains a selection of problems.

Morrison, Robert Thornton, and Robert Neilson Boyd. ORGANIC CHEMISTRY. 4th ed. Boston: Allyn & Bacon, 1983. An outstanding undergraduate textbook of organic chemistry that well surpasses this article. Yet it explains the basic concepts so clearly that it must serve as the final authority for questions the reader might have. Many problems of varying difficulty.

Van Tamelen, Eugene E. "Benzene: The Story of Its Formulas, 1865-1965." CHEMISTRY 38 (January, 1965): 6-11. To celebrate the one hundredth anniversary of the proposal of the currently accepted structural formula for benzene, van Tamelen describes his own studies with alternative structures and predicts future developments.

Carbon and Carbon Group Compounds

Chemical Formulas and Combinations

Isomeric Forms and Molecules