Accelerated dehydration of D-fructose performed in microdroplets by a commercial ESI Z-spray source

Besides its use as an analytical tool, mass spectrometry (MS) has long been employed in reaction monitoring to intercept elusive intermediates and highlight the mechanistic details of a chemical transformation. The introduction of electrospray ionization (ESI) by Fenn et al. [1] enables one to directly generate from a diluted aliquot of a reaction mixture a plume of charged droplets showing a diameter less than 1,0 μm. Once desolvated, the microdroplets release isolated ionic species that provide an accurate picture of the reaction progress in solution. Interestingly, the desolvation time of the charged droplets can be easily increased in the air by increasing the distance between the ESI source and the MS inlet. Such a dramatic change of the reaction conditions can indeed accelerate the reaction rate up to 105 times compared to the same process occurring in bulk [2]. As a consequence, the ionized reagents, typically detected by MS at short distances, are promptly replaced by the reaction intermediates or even by the ionized products. Since several milestone reactions of organic chemistry have recently benefited from acceleration in confined volumes [3], we studied the dehydration reaction of D-fructose in microdroplets under ambient conditions. Furan derivatives, such as 5-hydromethylfuraldehyde (5-HMF), are indeed produced by the acid-catalysed dehydration of hexoses, thus obtaining key-building block molecules from “green” resources [4]. To this end, we used a commercial ESI Z-spray source of a Q-TOF Ultima mass spectrometer already employed in our laboratory to successfully modify electrode surfaces by ambient ion soft landing experiments [5]. High conversion ratios of D-fructose into 5-HMF were obtained by using KHSO4 metal-free and green catalyst in millimolar concentrations. Nonetheless, the reaction outcome was found to be highly sensitive to the catalyst and solvents employed, as well as to the ionization and desolvation parameters of the ESI source. Further attempts to scale up the reaction for potential industrial application are actually in progress in our laboratory.