Direct Metal-Free Transformation of Alkynes to Nitriles: Computational Evidence for the Precise Reaction Mechanism

Abstract

Density functional theory calculations elucidated the precise reaction mechanism for the conversion of diphenylacetylenes into benzonitriles involving the cleavage of the triple C≡C bond, with N-iodosuccinimide (NIS) as an oxidant and trimethylsilyl azide (TMSN3) as a nitrogen donor. The reaction requires six steps with the activation barrier ΔG‡ = 33.5 kcal mol−1 and a highly exergonic reaction free-energy ΔGR = −191.9 kcal mol−1 in MeCN. Reaction profiles agree with several experimental observations, offering evidence for the formation of molecular I2, interpreting the necessity to increase the temperature to finalize the reaction, and revealing thermodynamic aspects allowing higher yields for alkynes with para-electron-donating groups. In addition, the proposed mechanism indicates usefulness of this concept for both internal and terminal alkynes, eliminates the option to replace NIS by its Cl- or Br-analogues, and strongly promotes NaN3 as an alternative to TMSN3. Lastly, our results advise increasing the solvent polarity as another route to advance this metal-free strategy towards more efficient processes.

Chemistry of Spontaneous Alkylation of Methimazole with 1,2-Dichloroethane

“…Thermal corrections were extracted from the corresponding frequency calculations, so that all of the presented results correspond to differences in the Gibbs free energies at room temperature and normal pressure. The choice of such computational setup was prompted by its success in reproducing various features of different organic [26,27], organometallic [28,29], and enzymatic systems [30,31], being particularly accurate for relative trends among similar reactants, which is the focus here. All transition state structures were located using the scan procedure, employing both 1D and 2D scans, the latter specifically utilized to exclude the possibility for concerted mechanisms.…”

Spectroscopic and Computational Study of the Protonation Equilibria of Amino-Substituted benzo[b]thieno[2,3-b]pyrido[1,2-a]benzimidazoles as Novel pH-Sensing Materials

“…Thermal corrections were extracted from the corresponding frequency calculations so that all value pertain to Gibbs free-energy differences at room temperature and normal pressure. The selection of such a computational approach was motivated by its accuracy in evaluating the reaction parameters and pK a values for a variety of analogous organic systems [26,27]. In this work, pK a parameters were obtained in an absolute way using the proton's gas phase free energy of G • (H + ) = 6.28 kcal mol −1 and its experimental aqueous-solution solvation free energy of ∆G SOLV (H + ) = −265.9 kcal mol −1 [28], also employed by Truhlar and colleagues [25] in parameterizing the utilized SMD model.…”

Novel Bis- and Mono-Pyrrolo[2,3-d]pyrimidine and Purine Derivatives: Synthesis, Computational Analysis and Antiproliferative Evaluation

“…Thermal corrections were extracted from the matching frequency calculations, so that all presented results correspond to differences in the Gibbs free energies at room temperature and normal pressure. The choice of such computational setup was prompted by its success in reproducing various features of different organic [65][66][67], organometallic [68,69] and biological systems [70,71], being particularly accurate for relative trends among similar reactants, which is the focus here. All transition state structures were located using the scan procedure, employing both 1D and 2D scans, the latter specifically utilized to probe the possibility for concerted mechanisms.…”