How a Breakthrough in a Dream Changed Chemistry Forever

Most of our nightly dreams are either traumatic conga lines of unresolved anxiety, or a hodgepodge of random, incoherent nonsense that makes perfect sense while we’re asleep but quickly fades into irrelevance once we awake. But for some people, dreams can be far more useful; indeed, they can change the world. Such was the case for German chemist August Kekulé, who in 1861 dozed off in front of his fireplace and awoke with the solution to a difficult theoretical problem. This is the story of how a dream changed chemistry forever.

Friedrich August Kekulé was born on September 7, 1829 in Darmstadt, Hesse, the son of civil servant Ludwig Kekulé. As a child he excelled at languages, drawing, and science, and was originally intended by his family to become an architect. However, while studying at the University of Geissen in 1848, he was – in his words – “seduced” by a lecture from the great chemist Justus von Liebig and decided to change careers. In 1850 he began working in von Liebig’s laboratory – where he studied the composition of gluten and wheat bran – before graduating with a doctorate in Chemistry in 1852. But as no teaching positions were then available, he continued his post-doctoral work in Paris, London, and Chur in Switzerland.

It was while working in London under chemist John Stenhouse that Kekulé first encountered the emerging field in which he would eventually make his name: organic chemistry. For centuries, scientists believed that “organic” substances produced by living organisms were fundamentally different from regular “inorganic” substances, being imbued with some kind of intangible “life force.” This doctrine was known as vitalism. In the early 19th Century, however, this view began to crumble as chemists demonstrated that supposedly “organic” molecules could be synthesized from inorganic ones in the laboratory. For example, in 1828, German chemist Friedrich Wöhler heated ammonium cyanate – a supposedly “inorganic” molecule – to produce urea. In a letter to fellow chemist Jacob Berzelius, Wöhler boasted that:

“In a manner of speaking, I can no longer hold my chemical water. I must tell you that I can make urea without the use of kidneys of any animal, be it man or dog.”

Chemists eventually realized that organic substances obeyed the same chemical rules as inorganic ones, but all had one thing in common: they were based on carbon, the fundamental building block of life on earth. Soon after this discovery, the newly-established field of organic chemistry began taking the world by storm. The emerging illuminating gas industry produced as a byproduct large quantities of a dark, sticky substance called coal tar, which chemists began probing in search of useful organic compounds. They were not to be disappointed. In 1856, British chemist William Perkin used coal tar to create the world’s first synthetic dye, mauvine, which not only revolutionized fashion but also laid the groundwork for the modern global chemical industry. Research into coal tar and other hydrocarbons soon yielded a veritable cornucopia of revolutionary products, from medicines to cosmetics, paints, and lubricants.

However, most of these early discoveries were made by blind trial and error, for chemists still did not fully understand how atoms came together to form molecules. In the early 19th century, chemists like Sir Humphry Davy had used electricity to split chemical compounds into their constituent elements, allowing their chemical formulae – that is, the number of each element within a given molecule – to be determined. Based on these experiments, Davy concluded that chemical compounds were composed of atoms of opposite charges, held together by electrostatic attraction. However, while this explanation worked well for simple compounds like sodium chloride – AKA table salt – it did not explain the vast number of substances composed of atoms with the same electric charge. Indeed, in many compounds an electrostatically positive atom like hydrogen could be replaced by an electrostatically negative one like chlorine with little change to the compound’s physical or chemical properties. Another mystery was how two or more compounds could have such different properties while being composed of the same elements. For instance, the compounds Propadiene, Propyne, and Cyclopropene all have the same chemical formula: C₃H₄.

In 1856, Kekulé was hired as an unsalaried lecturer at the University of Heidelberg, where he quickly distinguished himself as an energetic and highly original thinker and a much-respected teacher. In 1858 he moved to the University of Ghent in Belgium, and again in 1867 to the University of Bonn in Germany, where he would remain for the rest of his career. It was while at the University of Ghent that Kekulé made most of his major contributions to chemistry. Building on the observations of other chemists, Kekulé recognized that different atoms had different capacities to combine with other atoms – what Berzelius called atomicity but Kekulé dubbed valenz or “valency” – the term still used to this day. For example, hydrogen can only bond with one other atom and thus has a valence of one; sulfur has a valence of 2, Nitrogen 3, Carbon 4 and so on. Today, we know that valency results from the number of electrons in an atom’s outer electron shell, which can be shared with other atoms to form covalent bonds. Meanwhile, bonds formed by electrostatic attraction between oppositely-charged atoms are known as ionic bonds. Of course, in Kekulé’s day, the existence of atoms was purely theoretical and nothing was known of their structure. Nonetheless, the theory of valency proved extremely useful, with Kekulé theorizing that all organic compounds were built on a chain or “backbone” of carbon atoms linked together with single, double, or triple bonds. As carbon had a valency of 4, this allowed 1, 2 or 3 other atoms like hydrogen, oxygen, nitrogen, or chlorine to bond with each carbon atom.

Another idea that Kekulé incorporated into his theories was the concept of isomers, first proposed by Jacob Berzelius. Berzelius posited that the reason compounds with different properties could have the same chemical formula was that the atoms in each compound were arranged in a different geometric configuration. For example, Propadiene consists of a chain of three carbon atoms linked together with double bonds with two hydrogen atoms bonded to each end; while in Propyne the central carbon is single-bonded to one carbon and triple-bonded to the other, with one hydrogen atom bonded to one end of the molecule and three to the other. Finally, in Cyclopropene the three carbon atoms are linked not in a straight line but in a ring with one double and two single bonds, with two hydrogen atoms bonded to one carbon and one hydrogen to each of the other two. By combining the theory of valency with the theory of isomers, Kekulé posited that chemists should be able to work out the structure of every possible organic compound. It was simply a matter of swapping out different atoms in different locations on a molecule and noting the result. These ideas laid the groundwork for the field of structural chemistry, though Kekulé was not alone in this endeavour, with Scottish chemist Archibald Scott Couper and Russian chemist Aleksandr Butlerov developing similar theories at around the same time.

Kekulé published his ideas on structural chemistry in two groundbreaking articles published in 1858 as well as his popular textbook Lehrbuch der Organischen Chemie, first published in 1859. But while these works brought Kekulé much acclaim, not all his ideas were warmly received. For example, Kekulé developed a system for visually depicting valency and bonds between atoms in which monovalent atoms like hydrogen and chlorine were depicted as simple circles and polyvalent atoms like carbon and nitrogen as elongated ovals with multiple lobes. Chemists ridiculed these figures as “sausage formulae” and instead adopted the simpler “ball and stick” model developed by Scottish chemist Alexander Brown.

Kekulé’s theories allowed chemists to work out the structures of many common organic compounds, but the nature of one substance remained stubbornly elusive: Benzene.

Benzene has been known since the Sixteenth Century in the form of Benzoic Acid, produced by distilling the resin of the Styrax tree and used in perfumes and topical ointments. However, it was not until 1825 that British scientist Michael Faraday first isolated pure Benzene via the distillation of coal tar. By the time Kekulé began his research, Benzene was known to have the chemical formula C₆H_6. However, unlike other organic compounds chemists had studied thus far, Benzene did not follow the rules dictated by Kekulé’s valency and carbon backbone model. According to the former, carbon was tetravalent, meaning it could form bonds with four other atoms. Yet compared to other known organic compounds such as Methane – formula CH₄ – the Benzene molecule was strangely stable and unsaturated, containing far fewer hydrogen atoms than expected. This meant that many of the carbon atoms in the molecule had to be linked via double bonds. However, if Benzene was built around a chain of 6 carbon atoms, at least one bond had to be single, otherwise there would not be enough valencies left for the last two hydrogen atoms. This single bond, in turn, could exist in three different positions in the chain – centre, left, or right – meaning that Benzene should have two different structural isomers, each with the last two hydrogen atoms bonded at different positions in the carbon chain. Yet chemists could only ever find one isomer of Benzene. Furthermore, replacing one of the hydrogen atoms with another atom – for example, chlorine – should have produced two possible mono-substitution isomers: one with an end hydrogen substituted and one with a central hydrogen substituted. But again, only one such isomer could be found. It was a puzzle which threatened to undermine the entire foundation of organic chemistry.

It was then that Kekulé had one of the most famous revelations in the history of science – arguably on par with Archimedes’ alleged “Eureka!” moment or Newton’s fabled apple. As he later recounted in an 1890 lecture, the event occurred in Ghent during the winter of 1861, while Kekulé was working on his organic chemistry textbook:

“I was sitting writing at my textbook; but the work did not progress; my thoughts were elsewhere. I turned my chair towards the fire and dozed. Again the atoms were gambolling before my eyes. This time the smaller groups kept modestly in the background. My mental eye, rendered more acute by repeated visions of the kind, could now distinguish larger structures of manifold conformation: long rows, sometimes more closely fitted together; all twining and twisting in snakelike motion. But look! What was that? One of the snakes had seized hold of its own tail, and the form whirled mockingly before my eyes. As if by a flash of lightning I awoke; and this time I also spent the rest of the night in working out the consequences of the hypothesis.”

This was not the first time dreams had come to Kekulé’s aid. Allegedly, his ideas about the tetravalency of carbon were inspired by a daydream about “dancing molecules” he had aboard a London omnibus in 1855. Based on his second, more famous dream, Kekulé formed a bold new hypothesis: the Benzene molecule wasn’t linear, but ring-shaped, with an inner, hexagonal ring of six carbon atoms linked by alternating single and double bonds and six hydrogen atoms bonded to the outside. This theory solved nearly all the problems with the old linear model, explaining at a stroke why Benzene could be so unsaturated while remaining stable and why the molecule had only one structural and one mono-substitution isomer: as the molecule is rotationally symmetrical, all the hydrogen atoms are structurally equivalent to one another, meaning that substituting one is the same as substituting another.

But despite their elegance and power, Kekulé did not immediately publish his ideas. This delay was likely due to problems in Kekulé’s personal life. The year after his famous dream, Kekulé married Stephanie Drory, daughter of an English official in the Belgian illuminating gas industry. Tragically, Stephanie died only a year later while giving birth to the couple’s only son, sending Kekulé into a years-long depression during which he only carried out routine teaching work. It was not until 1865 that Kekulé finally resumed his research, and on May 11 of that year he presented his theory of the cyclical structure of Benzene in a historic paper titled Some Notes on Several Substitution Products of Benzene. In the paper, he predicted that if his theory were correct, Benzene should have three di-substituted isomers – that is, in which two of the hydrogen atoms are replaced: orthobenzene, in which two adjacent hydrogens are replaced; metabenzene, in which alternate hydrogens are replaced; and parabenzene, in which opposite hydrogens are replaced. Over the next few years, Kekulé and his colleagues soon succeeded in isolating all three isomers, further strengthening his theory.

Kekulé’s breakthrough revolutionized the field of organic chemistry, as the vast majority of organic compounds were found to contain one or more Benzene rings. Today, these are known as aromatic compounds. So influential was Kekulé’s discovery, that in 1890 the German Chemical Society organized an elaborate celebration to mark the 25th anniversary of his landmark 1865 paper. It was during this event that Kekulé first publicly recounted the story of his now-famous 1861 dream about snakes biting their tails. Whether this event actually happened or was merely a whimsical invention made after the fact has been debated, but as a dream cannot exactly be witnessed by others, we will never know. As a further honour, in 1895 Kekulé was ennobled by Kaiser Wilhelm II as August Kekule von Stradonitz. Interestingly, this title dropped the accent from the end of Kekulé’s, name, which had been added in 1806 so celebrate the annexation of the Grand Duchy of Hesse by Napoleon.

Yet despite their outsized influence, Kekulé’s theories were not without their detractors. For example, in 1872 one of Kekulé’s students, Albert Ladenburg, pointed out that Benzene should have two different ortho isomers depending on whether the two substituted hydrogen atoms were separated by a single or double carbon bond. In response, Kekulé proposed a dynamic model wherein the double and single bonds in the benzene ring continually swapped places, making every position in the ring structurally equivalent. But Kekulé was unable to put forward any plausible mechanism to explain this behaviour, leading Ladenberg and others to develop alternative molecular structures for Benzene. For example, Ladenberg’s proposed structure, prismane, took the form of two rings of three carbon atoms linked together to form a triangular prism, while British chemist James Dewar’s structure comprised two square rings of four carbon atoms linked together. However, both isomers were later synthesized and found to exhibit no Benzene-like properties. Then, in 1928, American chemist Linus Pauling proposed that the Benzene molecule resonated between two quantum-mechanical structures, producing the same effect as Kekulé’s dynamic model. Kekulé, it turned out, had been right all along.

Sadly, Kekulé’ professional success was not matched by his personal life. In 1867 he became a professor at the University of Bonn, where he would remain for the rest of his career. Nine years later, he married his housekeeper, Louise Hôgel, with which he had three more children. Unfortunately, the marriage proved an unhappy one, and Kekulé’s health soon began to fail. He died of influenza on July 13, 1896, aged 66. But Kekulé’s legacy lives on, for the aromatic compounds he helped discover form the basis of countless products which make our modern world possible, from plastics to medicines to fuels. And it all started with a dream.

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