Estimation of the nucleophilic α- and their relative β-, γ- and δ-effects in solution through fluorometry

Abstract

The α-effect is a mysterious phenomenon of the organic chemistry that allow to explain the significant reactivity of nucleophiles featuring an α-substituent. Its determination often requires of extensive kinetic analysis or studies in gas phase as well as the use of specific chemical reactions and specialized substrates. Herein we reported a simple and rapid strategy to validate the nucleophilicity and nucleophilic α-effect from simple steady state fluorescence measurements at room temperature with minimal sample and time requirements using a convenient fluorophore featuring an σ-hole region. The key points were the use of a fluorophore having a high intramolecular charge-transfer (ICT) and an electrophilic acceptor moiety along the donor (D)-acceptor (A) chain. The interaction of the nucleophile with the acceptor group upon excitation promoted a selective quenching that was dependent on the nucleophilicity of the nucleophile, whereas the existence of the ICT enhanced the selectivity and strength of the quenching response. It allowed us to generate a nucleophilic trend and recognize cases of α-effect. A broad number of nucleophiles from anionic species to neutral nucleophiles was analyzed. Also, we introduced the concept of “nucleophilic β, γ- and δ-effects” for interpreting the over-nucleophilicity of some “β-, γ- and δ-nucleophiles”. A general interpretation of the anomalous nucleophilic effects based on the extra stabilization of transition-state was provided. The intermolecular interaction between nucleophile and acceptor moiety was theoretically and experimentally supported. Our strategy opens new perspective for quantifying the nucleophilicity and their anomalous effects based on the recognition of non-covalent interaction using fluorometry as key technique.