Triazine-Based Cationic Leaving Group: Synergistic Driving Forces for Rapid Formation of Carbocation Species

Abstract

A new triazine-based cationic leaving group has been developed for the acid-catalyzed alkylation of O- and C-nucleophiles. There are two synergistic driving forces, namely, stable C═O bond formation and charge-charge repulsive effects, involved in the rapid generation of the carbocation species in the presence of trifluoromethanesulfonic acid (∼200 mol %). Considerable rate acceleration of benzylation, allylation, and p-nitrobenzylation was observed as compared to the reactions with less than 100 mol % of the acid catalyst. The triazine-based leaving group showed superior p-nitrobenzylation yield and stability in comparison to common leaving groups, trichloroacetimidate and bromide. A plausible reaction mechanism (the cationic leaving group pathway) was proposed on the basis of mechanistic and kinetic studies, NMR experiments, and calculations.

Development of a Storable Triazinone-Based Reagent forO-p-Methoxybenzylation under Mild Heating Conditions

“…Since our purpose was to investigate the functional group tolerance, these known alcohols were selected although their O - p -methoxybenzylation reactions under appropriate conditions were reported individually. The reaction of 2-bromoethanol ( 5b ), which is sensitive to bases and silver salts, provided 6b in 87% yield . The tert -butyldimethylsilyl (TBS) group of the primary hydroxy group in 5c survived during the O - p -methoxybenzylation to give 6c in 88% yield .…”

Cooperation of the Neutral and the Cationic Leaving Group Pathways in Acid-Catalyzed O-Benzylation of TriBOT

“…We previously carried out a kinetic study for the model compound of TriBOT, 2-benzyloxy-4,6-dimethoxy-1,3,5-triazine ( 1 , Scheme ), whose protonated form ( 1 -H + ) gave the benzyl cation species and LG 2 following first-order kinetics . We refer to this kind of reaction mechanism for triazine-based alkylating reagents as a neutral LG pathway, where resulting coproducts like DiBOT and 2 have no charge …”

“…However, interestingly, TriBOT decreased more rapidly than expected as shown in Figure , implying possible rate acceleration caused by the excess H + . We recently reported a new reaction mechanism of triazine-based alkylating reagents, a cationic LG pathway (Scheme ) where the carbocation species were generated rapidly from N , N′ -diprotonated triazines formed in the presence of excess H + with a small equilibrium concentration . We also provided the rate law for this pathway in the O -benzylation reaction on the basis of kinetic studies using a model compound.…”

“…10 We refer to this kind of reaction mechanism for triazine-based alkylating reagents as a neutral LG pathway, where resulting coproducts like DiBOT and 2 have no charge. 11 Herein we analyze the reaction profile of TriBOT (80 mM) with TfOH (40 mM), at 25 °C, to study the kinetics of TriBOT, which is still not clearly understood (Scheme 2). The final product from TriBOT is isocyanuric acid, formed due to the intermediates, DiBOT and MonoBOT (Scheme 2), also generating the benzyl cation species in the presence of TfOH.…”

“…We recently reported a new reaction mechanism of triazine-based alkylating reagents, a cationic LG pathway (Scheme 4) where the carbocation species were generated rapidly from N,N′-diprotonated triazines formed in the presence of excess H + with a small equilibrium concentration. 11 We also provided the rate law for this pathway in the O-benzylation reaction on the basis of kinetic studies using a model compound. Using the rate law, the decrease in [TriBOT] obs ([TriBOT-H + ]) after 137.9 min can be given by eq 1 if both the neutral and the cationic LG pathways were operative.…”