In considering these results it is important to place them in context relative to classic SNAr reactions, which involves the use of a suitably strong base to ionize the nucleophilic component (nucleophile ionization) prior to a rate-determining (RDS) addition step to the electrophile. This results in a stabilized anion intermediate (Meisenheimer complex) prior to elimination to afford the product (Scheme S2). 2a-c Base-mediated SNAr is common for less acidic nucleophiles like thiols, alcohols and carbon-based nucleophiles. A less common SNAr variant involves using a Lewis or Brønsted acid to ionize basic electrophiles (electrophile ionization) for reaction with weakly basic nucleophiles such as anilines, azoles, and amines (Scheme S2). Our control experiments support a hybrid mechanism, where proton transfer (PT) results in dual ionization (DI) of N1b and E1a prior to reaction; here termed PTDI SNAr (Scheme 2). Examples of 'PTDI SNAr' like reactions of functionalized heterocycles with sulfur-based nucleophiles (sulfinic acids, thiophenols, etc) have been previously reported, but lack mechanistic details (for examples, see Scheme S3). In turn, we sought to further characterize the mechanism in order to unify similar reactions and identify key differences to classic SNAr reactions. Kinetic and DFT Analysis. To support our mechanistic hypothesis, we performed reaction progress kinetic analysis (RPKA). The reaction between methyl 4-mercaptobenzoate (N3) and 2-amino-4-iodopyridine (E5) in DMSO was selected (vide infra) and monitored at varying equivalents and temperatures using Fourier Transform Infrared Resonance (FTIR) Spectroscopy. These data were then modeled with Reaction Lab software simulating the PTDI mechanism, which supports rate-limiting proton transfer (RLPT) preequilibrium (Keq = 10 -6 ) as the initial step (Figures S9-12. Of note, kinetic simulating the initial addition of N3 prior to proton transfer did not fit the rate data (Figures ). Initial RLPT pre-equilibrium is unique for several reasons, most notably because addition is the archetypal RDS for base-mediated SNAr reactions. 2a Additionally, while a RLPT has been characterized in some SNAr reactions with amine nucleophiles, proton transfer occurs after an initial addition step, thus providing no electrophile activation. This finding is also consistent with the observation that more acidic/less nucleophilic thiols (like N3) proceed with increased rate compared to less acidic/more nucleophilic thiols, and analogously with how less basic haloheterocycles (pKa<2) are not highly effective in this reaction (vide infra).