Experimental Determination of Activation Energy of Nucleophilic Aromatic Substitution on Porphyrins

Abstract

A physical organic chemistry experiment is described for second-year college students. Students performed nucleophilic aromatic substitution (NAS) reactions on 5,10,15,20-tetrakis­(2,3,4,5,6-pentafluorophenyl)­porphyrin (TPPF20) using three different nucleophiles. Substitution occurs preferentially at the 4-position (para) because it is thermodynamically favored, and the 2- and 6- (ortho) positions are kinetically disfavored because of steric interactions with the porphyrin ring. The activation energy depends heavily on the nucleophile. Open-source software (ImageJ from NIH) was used to quantify relative intensities of spots on a TLC plate obtained from different times and varying temperatures. These data were used to generate Arrhenius plots allowing students to determine relative activation energies for three different primary nucleophiles. The experiment was developed by 5 undergraduates and evaluated by 40 organic chemistry II students and 8 students in a physical chemistry laboratory. Students gained a deeper understanding of the relationships between the NAS mechanism, Arrhenius plots, and activation energy.

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

“…The subsequent analysis in the context of competing reaction pathways is not reported in the chemistry education literature. A literature search reveals experimental determination of transition state energies that focus on a single reaction pathway or infer thermochemical properties from quantum-chemical calculations. − To the best of our knowledge, this is the first undergraduate laboratory procedure that emphasizes product distributions when reactions are conducted under kinetic vs thermodynamic control by microwave-assisted techniques. Moreover, activation parameters (ΔΔ H ⧧ (≈ Δ E a ), ΔΔ S ⧧ , and ΔΔ G ⧧ ) are directly accessible by analysis of product ratios determined under kinetic control.…”

A Green Nucleophilic Aromatic Substitution Reaction

“…Latimer et al compared microwave-induced organic reaction enhancement to that of more traditional synthetic procedures toward S N Ar reaction . Rizvi et al determined the activation energy of S N Ar on porphyrins . Goodrich et al employed S N Ar reaction as one of the reactions in the synthesis of a fluorescent acridone …”

“…Even though aryl halides are generally inert to nucleophilic substitution, aryl halides that contain electron withdrawing groups such as a nitro group ortho or para to the halogen undergo nucleophilic aromatic substitution. Variations of S N Ar experiments have been developed for chemistry education in the past, each with distinct value. − For example, Santos et al developed a problem-solving and collaborative-learning approach to the synthesis of aryl-substituted 2,4-dinitrophenylamines to facilitate higher retention and encourage students to interpret and draw conclusions from data themselves . Avila et al redesigned the synthesis of 2-ethylbenzoic acid into a five-step microscale experiment .…”

“…39 Rizvi et al determined the activation energy of S N Ar on porphyrins. 40 Goodrich et al employed S N Ar reaction as one of the reactions in the synthesis of a fluorescent acridone. 41 Ambrose University, 42 a liberal arts university with smaller class sizes, is committed to the incorporation of green chemistry practices into chemistry laboratories with safer chemicals and processes.…”

Determining the Energy of Activation of a Salt, Water, and Alcohol Emulsion

“…This helps students understand (a) the relationship between temperature and reaction rate and (b) why spontaneous processes (such as combustion) often require an initial input of energy to get started. Many undergraduate-level laboratory experiments have been devised to determine the activation energy of chemical reactions using tools such as spectroscopy, , chromatography, calorimetry, , and even “levitating” magnetic beads to monitor solution density . These experiments are creative and well-designed and yield consistent results, but often they require the use of expensive equipment or clever mathematical manipulations that may be unnecessarily confusing for high school students and first-year college students.…”