Ortho effect in the Bergman cyclization: comparison of experimental approaches and dissection of cycloaromatization kinetics.
Four different experimental sources of kinetic information were combined to study the effect of ortho substituents on the rate of Bergman cycloaromatization. All methods confirm that the cyclization barrier is highly sensitive to the nature of the ortho substituents. However, the measured activation energies strongly depend on the choice of experimental technique: even the relative trends provided by the different methods agree with each other only in the case of acceptor substituents. Both the onset peaks and the activation energies determined by differential scanning calorimetry (DSC; either in neat enediynes or in their solutions in 10.6 M 1,4-cyclohexadiene (1,4-CHD)) strongly overestimate the reactivity of 1,2-diethynylbenzene, suggesting that DSC cannot be taken as a reliable indicator of enediyne reactivity. This discrepancy is likely to stem from the presence of side reactions with low activation barriers, especially important when the reaction is conducted in neat enediyne. On the other hand, kinetic measurements based on monitoring the concentrations of enediyne reactants and naphthalene products provide reliable general trends that include the parent benzannelated enediyne. These measurements confirm that both ortho-NO2 and ortho-CHO substituents substantially decrease activation energies for the Bergman cyclization, supporting earlier computational predictions. A comparison of theory and experiment suggests that computations at the Moeller-Plesset second-order perturbation theory (MP2)/6-31G level provide an excellent alternative to DFT when an accurate description of the contribution of noncovalent interactions to the activation energy is needed. Activation energies derived from k(eff), the effective rate constant under the pseudo-first-order approximation, depend on the 1,4-CHD concentrations. The true rate constant, k(1), for the cyclization step and the ratio of constants for the retro-Bergman ring opening, k(-1), and the intermolecular H-atom abstraction, k2, were determined from the dependence of cycloaromatization kinetics of ortho- and para-NO2 substituted enediynes on the concentration of 1,4-CHD.
Zeidan
Tarek A
TA
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA.
Kovalenko
Serguei V
SV
Manoharan
Mariappan
M
Alabugin
Igor V
IV
D000598:Amino Acids, Cyclic / Q000138:chemical synthesis / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003500:Cyclization; D053281:Enediynes; D005609:Free Radicals / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D009589:Nitrogen Oxides / Q000737:chemistry; D013696:Temperature
D000598:Amino Acids, Cyclic; D053281:Enediynes; D005609:Free Radicals; D009589:Nitrogen Oxides; D009584:Nitrogen