AbstractNiobium pentoxides are promising acid catalysts for the conversion of biomass into fuels and chemicals. Developing new synthesis routes is essential for designing niobium pentoxide catalysts with improved activity for specific practical processes. Here we show a synthesis approach in acetophenone, which produces nanostructured niobium pentoxides with varying structure and acidity that act as efficient acid catalysts. The oxides have orthorhombic structures with different extents of distortions and coordinatively unsaturated metal atoms. A strong dependence is observed between the type and strength of the acid sites and specific structural motifs. Ultrasmall niobium pentoxide nanoparticles, which have strong Brønsted acidity, as well as Lewis acidity, give product yields of 96% (3 h, 140 °C, 100% conversion), 85% (3 h, 140 °C, 86% conversion), and 100% (3 h, 110 °C, 100% conversion) in the reactions of furfuryl alcohol, 5-(hydroxymethyl)furfural, and α-angelica lactone with ethanol, respectively.