Some Like It Hot: Experimentally Determining ΔΔH^⧧, ΔΔS^⧧, and ΔΔG^⧧ between Kinetic and Thermodynamic Diels–Alder Pathways Using Microwave-Assisted Synthesis

Abstract

The effects of kinetic vs thermodynamic control on endo/exo stereoisomer ratios can be observed in a simple Diels−Alder reaction between Nphenylmaleimide and furan. The use of microwave-promoted synthesis affords the cycloadducts in yields ranging from 65−100%, employing reaction times of 1−10 min at temperatures of 55−130 °C. Short reaction times enable screening of numerous reaction conditions (time and temperature) within a single lab period, where endo:exo product ratios follow the primary facets of kinetic and thermodynamic control. Analysis of product ratios obtained under kinetic control allows for the evaluation of activation parameters (ΔΔH ⧧ (≈ ΔE a ), ΔΔS ⧧ , and ΔΔG ⧧ ) by means of the Arrhenius and Eyring equations. Values of ΔΔH ⧧ , ΔΔS ⧧ , and ΔΔG ⧧ were found to be 6.4 ± 0.3 kJ mol −1 , 16.5 ± 0.9 J mol −1 K −1 , and 1.5 ± 0.4 kJ mol −1 (ΔΔ: exo − endo), respectively. Experimentally determined activation parameters correlate well with quantum-chemical calculations. Several key teaching points are also addressed, including frontier molecular orbital analysis, reversibility of the Diels−Alder reaction, column chromatography, and the use of 1 H nuclear magnetic resonance spectroscopy to assess both stereoisomeric yield and purity.

Using Computational Chemistry to Improve Students’ Multidimensional Understanding of Complex Electrophilic Aromatic Substitution Reactions: Further Analysis of the Solvent Effect, Temperature Influence, and Kinetic Behaviors

“…− capturing the hydrogen atom on the newly substituted carbon atom leads to final products 3 and 4. 3,5…”

“…Next, M1 and M1* undergo the electrophilic aromatic substitution process with rate constants k 1 and k 2 to give the intermediates M2 and M2* , respectively. Subsequent deprotonation via AlCl 4 – capturing the hydrogen atom on the newly substituted carbon atom leads to final products 3 and 4 . , …”

“…Two reaction pathways are under kinetic control, and the reaction pre-equilibrium between M1 and M1 * is established. , …”

“…Student-centered teaching has become increasingly common in higher education in recent decades. After finishing the basic organic content in classes or lectures, students in universities tend to utilize both experiments and theories to further strengthen learning outcomes and to obtain deep understanding of a series of chemical reactions. − With the rapid development of science and technology, higher-level interdisciplinary requirements for the depth, extension, and diversity of chemistry learning are indispensable. In this regard, some new methods such as computational chemistry and molecular dynamics simulations have been introduced into chemistry education in universities, and various computational chemistry methods are widely put into applications. − Among them, DFT (density functional theory) could be used to study structures and properties of multielectron molecules in terms of the electron density, and it is now widely used in organic chemistry scientific research. ,− …”

Thermodynamics and Stereochemistry of Diels–Alder Polymer Networks: Role of Crosslinker Flexibility and Crosslinking Density

“…One such factorstereochemistry of DA adductsstems from the two isomers, endo and exo derivatives, dissociating at significantly different temperatures. , Previously, we demonstrated that selective dissociation of endo and exo DA adducts occurs in solvent-free networks and the conversion between endo and exo adducts through thermal annealing can be used to efficiently reconfigure the permanent shape of such polymer networks. Although the stereochemistry of the DA reaction is documented for reactions in dilute solutions of low-molecular-weight compounds, ,− a clear understanding for solvent-free polymer networks is lacking. Reactions involving polymer chains are associated with conformational entropy changes , and the entropic effects of the crosslinking network on DA reaction are expected to be significant.…”