Kinetic and Mechanistic Study of Aldose Conversion to Functionalized Furans in Aqueous Solutions

Abstract

Reaction mixtures of naturally abundant aldoses and CH nucleophiles allow for the formation of functionalized furan precursors using low temperatures and metal-free catalysis in aqueous solutions of dilute base catalysts. We employ in situ NMR assays to clarify the mechanism and kinetics of the conversion. Catalysis serves a double role in ring-opening of stable aldoses such as glucose and xylose and facilitating the subsequent reactions with CH acids such as malononitrile or cyanoacetamide. Resultant acyclic products are shown to convert quickly to a monocyclic product prior to the slower formation of a more stable bicyclic intermediate and dehydration to tri-functionalized furan. Especially the reversible 5-exo-dig ring closure entailing oxygen attack onto a nitrile carbon is surprisingly fast with an equilibrium vastly towards the cyclic state, sequestering reactive groups and allowing the selective conversion to tri-functionalized furan. The reaction hinges on the fast formation of intermediates without CH acidity and competes with the oligomerization of CH nucleophiles. Insight derived from in situ NMR analysis shows the prowess of high-resolution in situ spectroscopy in clarifying the interplay between catalysts and reactants. Such insight will be vital for the optimization of reactions that upgrade biorenewables under benign conditions.

Tailoring the Formation of Functionalized Furans from Glucose in Water with Nature-Sourced Catalysts and In Situ NMR

“…glucopyranose was paralleled by the Knoevenagel addition and rapid cyclization to 2 as previously observed for the triethylamine catalyzed conversion [37]. Hence, ring opening was a limiting step for the Knoevenagel addition under MgO catalysis.…”

“…To gain additional mechanistic insight into the reaction, the conditions were modified to use 0.05 equivalents of the catalyst at 298 K (Figure 2b,c). Under these conditions, it was evident that mutarotation of the α-glucopyranose substrate to β-glucopyranose was paralleled by the Knoevenagel addition and rapid cyclization to 2 as previously observed for the triethylamine catalyzed conversion [37]. Hence, ring opening was a limiting step for the Knoevenagel addition under MgO catalysis.…”

“…Building on previous work describing the Knoevenagel reaction between aldoses and malononitrile using triethylamine catalysis [ 24 , 37 ], we started by tracking the reaction in the presence of MgO as the catalyst. MgO is a cheap and recyclable base catalyst that has been used both for glucose isomerization to fructose [ 15 ] and for the Knoevenagel reaction to the bicyclic dihydrofuran derivative 3 [ 30 ].…”