An Improved Mechanistic Interpretation of the Acid-Catalyzed Dehydration of Methylcyclohexanols

Brian Esselman

The acid-catalyzed dehydration of regioisomeric methylcyclohexanols is a classic organic chemistry experiment featured in a variety of laboratory textbooks and literature.  The mechanistic details of this reaction have received an inconsistent and occasionally inaccurate treatment, wherein the reaction has been described as a mix of E1, E2-like, acid-catalyzed E2, and base-catalyzed E2 processes.  We provide an overview of how this reaction has been represented in the chemistry education literature and describe a model for its mechanistic interpretation as an E1 reaction that is typically analyzed before thermodynamic equilibrium is established.  This model is supported by new experimental data and computational explorations of the reactive intermediates and cycloalkene products.  We provide clear recommendations for how this reaction should be presented to students.

Explaining how and why phenomena occur is at the heart of all scientific disciplines.   Thus, the use of authentic spectroscopic data to enable students to identify and rationalize the outcome of a chemical reaction is the foundation of an effective laboratory curriculum.  Wherever possible, this task should be supported by computational chemistry, because of its ability to provide insight into the electronic structures and energies of the species involved.  The availability and speed of modern instrumentation provides instructors and students the ability to acquire large amounts of authentic data, while greater access to computational chemistry software packages and cheaper hardware makes theoretical results more accessible to students.  Thus, it is incumbent on chemistry instructors to find effective ways to combine these tools to support students in their journey toward making sense of chemical systems.

Studies on the acid-catalyzed dehydration of methylcyclohexanols are prominent in the chemistry education literature, and this reaction is also featured in several organic laboratory textbooks, likely due to its operational simplicity, inexpensive reagents, and utility as a prototypical E1 reaction system.   This process is complex and generates a range of alkenes (some likely expected by students, others less so) that can be detected via routine NMR and GC-MS analysis.  For example, the dehydration of cis and trans-2-methylcyclohexanol has been reported to yield up to seven regioisomeric alkenes, affording instructors and students the opportunity to explore the complex nature of carbocation-featuring reactions.  Inspection of authentic GC-MS or NMR data makes it clear to students that the simple notion of a 2° carbocation always rearranging to form a more stable 3° carbocation does not explain the range of observed alkene products.  To rationalize this system, students and instructors must adopt a more appropriate model for carbocation reactivity that includes facile rearrangements of 2° carbocations to not only 3° carbocations but also to other 2° cations that can also involve ring expansions and contractions.  Unfortunately, the rationalizations presented in previous studies incompletely explained the observed data.  In some cases, the explanations were inconsistent with well-established models/concepts of the undergraduate organic chemistry curriculum (carbocation stability/reactivity, conformational analysis, reversibility/irreversibility of reactions, potential energy surfaces, acid/base chemistry, transition state theory, etc.)

We sought to clarify the mechanism of this set of dehydration reactions by analysis of the available experimental data and application of modern computational methods.  Our goal was to obtain a clearer understanding of the reaction system so that it might entice other laboratory instructors to embrace the complexity of these reaction and allow their students to explore them.  The acid-catalyzed dehydration of methylcyclohexanols has been described previously as a mix of E1, E2-like, acid-catalyzed E2, and base-catalyzed E2 processes, however, all the experimental spectroscopic evidence (GC-MS and NMR) can be rationalized via an E1 reaction that has typically been analyzed before thermodynamic equilibrium is established.  (The system does have a delightful feature wherein one of the protonated 2-methylcyclohexanol stereoisomers can undergo simultaneous dehydration and hydride shift, thus bypassing 2° carbocation formation!)  If well-scaffolded, a mechanistic model that explains all of the observed data from this reaction is accessible to undergraduates.

In addition to introducing students to a deceptively complex chemical system, this exercise also serves as a case-study for laboratory instructors seeking to incorporate authentic computational chemistry into their curricula.  Rather simple calculations can provide the relative energies of the cycloalkenene products generated in these reaction and, pedagogically, this would serve to reinforce ideas introduced in lecture regarding alkene stability trends and ring strain.  Such calculations, however, are only relevant to a system under thermodynamic control (i.e., where the relative energies of the products determine the relative ratio of those products).  If the dehydrations of 1-, 2-, 3-, and 4-methylcyclohexanol were under thermodynamic control, each reaction would produce the same products in the same ratios.  This is not the case and thus the relative energies of the products alone cannot explain the observed outcome.  Computational chemistry can provide insight into this system, but only when properly applied to the relevant portion of the potential energy surface the cationic intermediates.  When the reaction is kinetically controlled, instructors and students must focus on the high energy intermediates or transition states in order to adequately rationalize the observed outcome.  By focusing student explanations on the relevant portion of the potential energy surface of each reaction, instructors can support a broader narrative about how the energetics of organic reactions determine their outcome in a predictable manner.

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