S_N2 Fluorination reactions in ionic liquids: a mechanistic study towards solvent engineering

Abstract

In the catalysis of S(N)2 fluorination reactions, the ionic liquid anion plays a key role as a Lewis base by binding to the counterion Cs(+) and thereby reducing the retarding Coulombic influence of Cs(+) on the nucleophile F(-). The reaction rates also depend critically on the structures of ionic liquid cation, for example, n-butyl imidazolium gives no S(N)2 products, whereas n-butylmethyl imidazolium works well. The origin of the observed phenomenal synergetic effects by the ionic liquid [mim-(t)OH][OMs], in which t-butanol is bonded covalently to the cation [mim], is that the t-butanol moiety binds to the leaving group of the substrate, moderating the retarding interactions between the acidic hydrogen and F(-). This work is a significant step toward designing and engineering solvents for promoting specific chemical reactions.

New insights on reaction pathway selectivity promoted by crown ether phase-transfer catalysis: Model ab initio calculations of nucleophilic fluorination

“…Because of the importance of fluorination reactions in the synthesis of compounds of pharmaceutical interest [21][22][23][24], considerable efforts have been made towards the development of efficient fluorination reactions [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The reaction of fluoride ions with alkyl halides is known to proceed both by S N 2 nucleophilic substitution and E2 elimination pathways.…”

Tri–tert‐Butanolamine as an Organic Promoter in Nucleophilic Fluorination

“…tert ‐Butanol functionalized amines 1–3 were prepared by modifying the procedure reported by Mun et al. (Scheme ) . A solvent‐free reaction of isobutylene oxide and substituted ethylamine or ammonia at 50 o C for 4 days yielded quantitatively the corresponding Tri‐ tert ‐butanolamine [(tri‐ t BuOH)A, 1 ], 1‐[Ethyl (2‐hydroxy‐2‐methylpropyl) amino]‐2‐methyl propan‐2‐ol [(di‐ t BuOH)EtA, 2 ], and 1‐(Diethylamino)‐2‐methyl‐2‐propanol [(mono‐ t BuOH)EtA, 3 ].…”

Harnessing Ionic Interactions and Hydrogen Bonding for Nucleophilic Fluorination

“…Besides being considered excellent solvent for chemical reactions because of its many useful physicochemical properties such as very low vapor pressure, non-combustibility, high thermal stability, low viscosity, easy recovery and high ionic conductivity, ionic liquids (ILs) [10][11][12][13][14][15][16][17][18][19] have found further significant role as catalysts/promoters [20,21] in many chemical transformations such as S N 2 [22][23][24][25][26][27][28], Diels-Alder [29], aldol condensation [30], Heck [31][32][33], and Michael addition [34] reactions. The acceleration of reaction rates of organic reactions by IL occur by the nature of the substance comprising cation and anion.…”