<i>N,N</i>‐Dimethylhydrazine as a Reversible Derivatization Agent to Promote the Hydroxymethylation of Furfural with Formaldehyde

In this report, the synthesis of 5-hydroxymethylfurfural from concentrated feeds of two low-cost and industrially abundant chemicals: Furfural and formaldehyde is explored. By adjusting the acidity of the solvent, an alternative mechanism is discovered in which the reaction selectivity stops to the hydroxymethylation step, in contrast to previously reported acid-catalyzed pathways leading to the formation of the bisfuranic dimer as a major product. One of the keys of this study relies on the reversible derivation of the -CHO group of furfural with N,N-Dimethylhydrazine which plays a dual role: (1) it restores the nucleophilicity of the furan ring and (2) it reacts with HCHO to form in situ an electrophilic zwiterrionic species stabilized through hydrogen transfer. By means of experimental and theoretical investigations, this reaction is optimized and it is discovered that guaiacol can be used as a bio-based and safe solvent. Under optimized conditions, the hydroxymethylation of the furan ring of furfural occurs with more than 95% selectivity, at only 50 °C and with a stoichiometric amount of HCHO. A concentrated feed of furfural as high as 40 wt% in guaiacol can be employed without impacting the reaction selectivity, leading to an improvement of the reactor productivity to about 25 kg m^-3 h^-1. The recovery of the reaction products and the recycling of the N,N-dimehylhydrazone are also discussed.