Multicomponent Reactions of β‐Ketosulfones and Formaldehyde in a Bio‐Based Binary Mixture Solvent System Composed of Meglumine and Gluconic Acid Aqueous Solution

A mixture of two bio‐based chemicals, meglumine and gluconic acid aqueous solution (GAAS, 50 wt%), was demonstrated to be a task‐specific bio‐based solvent for performing the hydroxymethylation of β‐ketosulfones with formaldehyde. The formed hydroxymethylation product could further react with a nucleophile, which allowed us to develop some one‐pot, stepwise, three‐component reactions of β‐ketosulfones and formaldehyde in this binary mixture. Particularly, a one‐pot, two‐step, sequential four‐component reaction of α‐bromo ketone, sodium benzenesulfinate, thiophenol and formaldehyde was also developed. These results not only demonstrate that it is possible to develop a new bio‐based system by mixing two or more bio‐based chemicals together, but also confer us a convenient means for controlling the selectivity of some multicomponent reactions of formaldehyde. Because GAAS and meglumine are both highly hydrophilic, the mixed solvent system could thus be recovered after extraction of organic products. In a three‐component reaction of β‐ketosulfone, paraformaldehyde and α‐methylstyrene, the GAAS/meglumine system could be reused at least four times without significant loss of activity.