Proton transfer reactions of a bridged bis‐propyl bis‐imidazolium salt

Abstract

Tetraazafulvalene 1 has found broad application in reduction and other related transformations and is conveniently generated from bis‐propyl bis‐imidazolium salt 4 with a strong base in a non‐protic solvent. The proposed mechanism for the formation of 1 involves initial deprotonation at C(2) to give a mono‐carbene 9 followed by intramolecular reaction at the second azolium centre. Herein, we report the second‐order rate constants for deuteroxide‐catalysed exchange in aqueous solution of the C(2)‐hydrogens of bis‐propyl bis‐imidazolium di‐iodide salt 4 and related monomeric dipropyl imidazolium iodide 10 of kDO = 1.37 × 104 and 1.79 × 102 M−1 s−1, respectively, and used these data to calculate pKa values of 21.2 and 23.1. The greater C(2)‐H acidity of the doubly bridged bis‐propyl bis‐imidazolium salt 4 relative to 10 may be attributed to the inductive or electrostatic destabilization of the conjugate acid dicationic azolium ion 4 relative to the monocationic carbene 9, which is enhanced by bis‐tethering. Formation of tetraazafulvalene 1 was not observed under the aqueous conditions employed highlighting that carbene reprotonation significantly outcompetes dimerization under these conditions. Copyright © 2016 John Wiley & Sons, Ltd.

Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation

“…For both 6 and 7, reactions were too fast above pD 4 for NMR analysis. The kinetic and NMR methods used for the analysis of the C(3)-H/D exchange reactions described herein were identical to those reported by us previously [60,61,63,64]. Over time, the disappearance of the singlet at ~10.3 ppm due to the C(3)-H is observed; however, there is no change in the integrals of all other signals, nor in the appearance of new signals.…”

“…The reactivities to deprotonation by a common base, kDO, allow for the evaluation of the protofugalities of the C(3) hydrogens in the series of triazolium ions. In our previous studies, kDO values for N-aryl triazolium ions spanned a range of 30 fold across the large series [60][61][62][63][64]. Maximal kDO values (8  10 8 M −1 s −1 ) were observed for N-pentafluorophenyl-substituted triazolium salts, whereas the lowest value to date of 4.2  10 7 M −1 s −1 was observed for an N-4-methoxyphenyltriazolium salt 16.…”

“…Owing to the greater basicities of most NHCs relative to hydroxide ion, quantitative deprotonation of water occurs, which prevents the determination of pKa values by direct quantification of the relative concentrations of acid and conjugate base species at equilibrium. We previously employed an alternative kinetic approach by using the rate constants for the forward and reverse directions of the proton transfer equilibrium in the calculation of pKa using Equation 6 derived for Scheme 2 [60,61,[63][64][65]. In this equation, kHO (M -1 s -1 ) is the second-order rate constant for deprotonation at C(3) by hydroxide ion, which may be calculated from the corresponding kDO value using a value of kDO/ kHO = 2.4 for the secondary solvent isotope effect on the basicity of HO − in H2O versus DO − in D2O.…”

“…For example, the N-pentafluorophenyl catalyst 4 designed by Connon and Zeitler still holds the record, to our knowledge, of being the most efficient and stereoselective catalyst for the asymmetric benzoin reaction [47]. As the initial proton transfer step for the formation of triazolylidene 2 is common to a broad range of transformations, we reported both rate constants for deprotonation (kinetic acidities or protofugalities [59]) and carbon acid pKa values for a large series of triazolium salts in aqueous solution, which included 36 N-aryl examples [60][61][62][63][64]. In addition, there is an increasingly large body of literature data pertaining to the pKa values of the conjugate acids of NHCs in a range of solvents [65][66][67][68][69][70][71][72][73][74][75].…”

Substituent Effects on Carbon Acidity in Aqueous Solution and at Enzyme Active Sites

“…31 The value of p K a = 18.9 reported for the carbon ionization of the 3,4-dimethylthiazolium cation (chart 2) shows that thiazolium cations are stronger carbon acids than similarly substituted imidazolium cations. 32 Recent reports from the literature provide examples of the scope for studies on substituent effects on these carbon acid p K a s. 33 …”