A Robust, “One-Pot” Method for Acquiring Kinetic Data for Hammett Plots Used To Demonstrate Transmission of Substituent Effects in Reactions of Aromatic Ethyl Esters

Abstract

A "one-pot" method for acquiring kinetic data for the reactions of a series of substituted aromatic esters with potassium hydroxide using 13 C NMR spectroscopy is described, which provides an efficient way to obtain sufficient data to demonstrate the Hammett equation in undergraduate laboratories. The method is time-efficient and robust, and lends itself to group work. The high throughput nature of the method allows collection of sufficient data to explore the transmission of electronic effects between the aromatic moiety and the ester functionality with varying chain lengths.

Ionic liquid effects on a multistep process. Increased product formation due to enhancement of all steps

“…1) is linear (R 2 = 0.985), with gradient (or reaction constant, ρ) = 2.92 ± 0.09 indicating that this addition step is very susceptible to the electronic nature of the substituent. 59,60 It should be noted that it is feasible to separately fit the rate constants for σ p ≤ 0 and σ p > 0, and this results in large, positive ρ values for both fits (ρ = 3.19 ± 0.12 and ρ = 2.17 ± 0.06, respectively, Fig. Uncertainties quoted represent the standard deviation of three replicates moving to the transition state.…”

“…This trend is exactly as would be expected for this reaction type, and is consistent with related nucleophilic additions to carbonyl groups. 59,60 It should be noted that it is feasible to separately fit the rate constants for σ p ≤ 0 and σ p > 0, and this results in large, positive ρ values for both fits (ρ = 3.19 ± 0.12 and ρ = 2.17 ± 0.06, respectively, Fig. S9 †).…”

Rhodium-Catalyzed C–H Amination: A Case Study of Selectivity in C–H Functionalization Reactions

“…A more accurate method for quantifying relative reaction rates in competition experiments measures consumption of the two starting materials (see Notes to Instructors in the Supporting Information). Such an analysis is problematic for this lab due to the volatility of certain ethylarenes, particularly ethylbenzene. Fortunately, the error introduced by product ratio analysis manifests principally in the extreme data points of the Hammett plot (e.g., −OMe, −NO 2 ).…”

A broadly applicable quantitative relative reactivity model for nucleophilic aromatic substitution (SNAr) using simple descriptors

“…To complement the existing S N Ar rate data from the literature, we measured relative reaction rates for 74 individual electrophilesincluding many nitrogen heterocycles relevant to pharmaceutical synthesisusing a competition experiment approach, which is commonly used to generate univariate Hammett plots. [76][77][78][79][80][81] Having control over the composition of our training set gives us the exibility to have a varied and balanced distribution of structural features, which is necessary to ensure both accuracy and applicability in making new predictions. To make the model easy to implement, and to reduce the computational cost required, we combined simple and easy-to-obtain ground state molecular descriptors with our own experimentally determined S N Ar rates.…”