For decades, kekulene existed more in theory than in the lab, a tantalizing puzzle that challenged our fundamental understanding of carbon chemistry.
Six localized aromatic sextets
Global superaromaticity
Imagine a molecular doughnut made entirely of carbon atoms, a ring of fused benzene rings that has puzzled scientists for over forty years. This is kekulene, one of the most iconic molecules in organic chemistry. First synthesized in 1978, this macrocyclic wonder remained largely inaccessible and poorly understood until very recently.
The central question was simple yet profound: how are its electrons arranged? Does it behave as a single superaromatic system or as six separate benzene rings? For decades, the technology to answer this question did not exist. Now, thanks to a scientific detective story combining chemical ingenuity and cutting-edge microscopy, we finally have the answer.
Kekulene is a cycloarene, a fascinating family of polycyclic aromatic hydrocarbons where carbon atoms are arranged in a circular, donut-like shape. Its molecular structure (C48H24) consists of twelve benzene rings annelated into a giant cycle, forming a hexagonal macrocycle with a central cavity lined with hydrogen atoms.
For forty years after its first synthesis, the experimental evidence to definitively support one model over the other was lacking, leaving a significant gap in our understanding of this iconic molecule1 .
The breakthrough came in 2019 when a team from CiQUS (University of Santiago de Compostela) collaborated with IBM Research Zurich to tackle kekulene's mystery using a powerful combination of improved synthesis and state-of-the-art microscopy4 .
The first hurdle was simply obtaining the molecule. The original 1978 synthesis was a monumental achievement but was notoriously challenging and low-yielding, which is why it had apparently never been repeated1 . The researchers developed a new, improved synthetic route.
Their key innovation was constructing a crucial intermediate, 5,6,8,9-tetrahydrobenzo[m]tetraphene (2), in just one step. They achieved this via a double Diels-Alder reaction between styrene and a benzodiyne synthon, which is commercially available.
This improved the yield for this key intermediate four-fold compared to the original method, finally providing sufficient material for further study1 .
With kekulene in hand, the team turned to ultra-high-resolution Atomic Force Microscopy (AFM). This technique, which uses a sharp tip terminated with a single carbon monoxide molecule to achieve spectacular resolution, can image the structure of single molecules.
| Step | Description | Significance |
|---|---|---|
| Improved Synthesis | One-step double Diels-Alder reaction to create a key intermediate | 4-fold yield increase; made study feasible1 |
| Sample Deposition | Sublimation onto a Cu(111) surface at 10 K | Isolated and immobilized individual molecules1 |
| AFM Imaging | Used a CO-functionalized tip for ultra-high resolution | Achieved bond-level resolution to measure electron density1 |
| Computational Validation | Simulated AFM images based on theoretical models | Provided a direct comparison to confirm experimental data1 |
What emerged from this process were the first-ever bond-resolved images of individual kekulene molecules. The researchers could clearly see the hexagonal macrocycle, but more importantly, they could distinguish variations in the bond lengths between carbon atoms.
The AFM images provided the definitive evidence that had eluded scientists for decades. The analysis of the bond-order contrast, which is directly related to bond length, showed a clear pattern of alternating single and double bonds. This pattern matched perfectly with the Clar model, revealing kekulene as a molecule with six localized aromatic sextets and no global superaromatic ring current1 4 .
| Ring Type | HOMA Value* | Aromaticity Interpretation |
|---|---|---|
| Ring A | 0.65 | Moderate aromaticity5 |
| Ring B | 0.92 | High aromaticity5 |
| Annulene Path | 0.77 | Moderate aromaticity5 |
| Annulene Path | 0.80 | Moderate aromaticity5 |
*HOMA (Harmonic Oscillator Model of Aromaticity): A value of 1 indicates perfect aromaticity, while lower values indicate weaker stabilization.
This conclusion was further supported by a separate 2020 study that took a different approach. Researchers performed an on-surface synthesis of kekulene directly on a copper substrate, creating a full ordered monolayer. Using angle-resolved photoemission spectroscopy (ARPES), they probed the molecule's highest occupied molecular orbital (HOMO). The measured orbital structure again aligned with the Clar model, providing complementary electronic evidence for the bond-localized structure5 .
The investigation of complex molecules like kekulene relies on specialized reagents and advanced techniques.
A commercially available building block that generates a highly reactive intermediate with two triple bonds, enabling the efficient construction of the kekulene backbone in one step1 .
A fluoride source used to trigger the generation of the reactive benzyne intermediate from the bistriflate precursor1 .
A simple hydrocarbon used as a diene component in the critical Diels-Alder reaction1 .
The key to ultra-high-resolution imaging. The single carbon monoxide molecule at the tip acts as a super-fine probe to feel the subtle forces of the molecule's electron cloud, making individual bonds visible1 .
The resolution of kekulene's structure is more than just the end of a forty-year debate. It highlights the incredible power of modern experimental techniques to visualize and understand matter at the atomic scale. Furthermore, this foundational knowledge opens new doors.
Kekulene and related cycloarenes are now considered model systems for designing graphene pores1 . Their well-defined structures and electronic properties can inform the creation of new two-dimensional carbon materials with tailored characteristics for applications in electronics, optoelectronics, and filtration.
Recent computational work even suggests that incorporating azulenoid kekulene units into graphene lattices could lead to some of the most stable 2D carbon allotropes known, potentially opening pathways to novel semiconductors.
The story of kekulene is a powerful reminder that in science, some of the most beautiful mysteries are worth revisiting. With patience, ingenuity, and new tools, today's scientists can finally answer the questions that puzzled the generations before them.