Hydrophilically functionalized pyrazoles from sugars

An effective and convenient protocol has been developed for the conversion of d-glucose and 6-O-α-d-glucopyranosyl-d-fructose (palatinose®, isomaltulose) into 5-[(1′S)-1′,2′-dihydroxyethyl]-1-phenylpyrazole-3-carboxaldehyde (4) and 5-[(1S)-2-(α-d-glucopyranosyloxy)-1-hydroxethyl])-1-phenylpyrazole-3-carboxaldehyde (5), key steps being the acetic anhydride-promoted dehydrative cyclization of the respective phenylosazones, and subsequent liberation of the N-acetylphenylhydrazone-blocked aldehyde function. Exploitation of the ensuing chemistry of 4 and 5 led to a variety of pyrazole building blocks with a diverse level of hydrophilic substituents (hydroxymethyl, dihydroxyethyl or glucosyl residues) and useful functional groups, such as chloro, cyano, aminomethyl, vinyl and acryloyl moieties.