Experimental Technology and Management

[Objective] Traditional organic synthesis reactions are usually conducted in flasks or reactors, where the detection of reaction intermediates relies on time-consuming offline analyses, making real-time characterization difficult in conventional laboratory courses. Recent studies have shown that organic reactions can be dramatically accelerated in electrospray droplets, with some proceeding to completion instantaneously during ionization under ambient conditions. Compared with traditional synthesis, this greatly shortens reaction time. Thus, the electrospray ion source serves as both an ionization tool and a microreactor, enabling “on-source synthesis” and the online capture of transient intermediates. When coupled with tandem mass spectrometry(MS/MS), the captured intermediates can be structurally validated. This study aims to develop a simple and efficient online analysis platform for capturing reaction intermediates and to integrate it into experimental teaching. [Method] Carbon fiber paper spray and electrospray ionization were innovatively employed as reaction inlets. The platform supports rapid on-source reactions, in which two reactants are instantaneously mixed and reacted within paper-spray or needle-spray droplets. It simultaneously enables in situ, real-time capture and structural verification of intermediates. The ion source offers several advantages, including simple assembly, reusable carbon fiber substrates, low cost, and high reproducibility and sensitivity. These features make it particularly well suited for investigating on-source organic reactions and mechanisms in undergraduate laboratory teaching. The device was applied to the synthesis of aryl phenols from arylboronic acids and hydrogen peroxide. Hydrogen peroxide solution was introduced through the electrospray needle, with water as a blank control. [Results] Based on mass spectrometry results, the reaction between arylboronic acid and H_2O₂ is inferred to proceed through two mechanisms. The first is an ionic pathway, where the lone electron pair of the peracidate anion attacks the boron atom of the boronic acid to form a Lewis acid–base complex. This complex undergoes aryl migration and eliminates a hydroxide ion to generate a boronic acid aryl ester. Under basic conditions, the boronic acid aryl ester is hydrolyzed, ultimately producing a phenoxide anion and boronic acid. The key experimental evidence supporting this pathway is the detection of characteristic intermediate signals at [M + 31]⁻(Lewis complex) and its dehydration product at [M + 15]⁻(corresponding to the boronic acid aryl ester or a related species) in the mass spectra of all tested substrates. These assignments are further confirmed by MS/MS fragmentation patterns. The second mechanism is a radical pathway, where H_2O₂ initially generates a peroxy radical anion that coordinates with arylboronic acid to form a radical adduct, corresponding to the characteristic intermediate signal at [M + 32]^-·. This radical intermediate subsequently undergoes single-electron transfer, rearrangement, and hydrolysis, ultimately yielding the phenoxide anion and boronic acid as well. [Conclusions] This study demonstrates the successful on-source synthesis of aryl phenols and the capture of key intermediates using electrospray-assisted carbon fiber paper spray ionization mass spectrometry, systematically revealing the coexistence of ionic and radical pathways. The method enables millisecond-level mixing and reaction in droplets, reducing the traditional reaction time of ～2 h to less than 2 min, and allows online structural validation of intermediates without the delays associated with offline analysis. Students not only acquire essential skills in mass spectrometer operation through ion source assembly and parameter optimization but also develop mechanistic reasoning by analyzing intermediate signals obtained from different substrates. The high instructional efficiency of this experiment transforms organic synthesis and mechanistic studies into a feasible, comprehensive teaching module that addresses the challenge of capturing short-lived intermediates while providing multidimensional training in experimental design, real-time monitoring, and mechanistic validation.