Acid-base-catalysed condensation reaction in water: isoxazolines and isoxazoles from nitroacetates and dipolarophiles.

Elena Trogu, Claudia Vinattieri, Francesco De Sarlo, Fabrizio Machetti

Index: Chemistry 18(7) , 2081-93, (2012)

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Abstract

Base-catalysed condensation reactions of nitroacetic esters with dipolarophiles to give isoxazole derivatives proceed faster, and often with higher yields, in the presence of water than in organic solvents such as chloroform. Kinetic profiles show that induction times are greatly reduced when the reaction is performed "in water" or "on water". Any specificity of the base related to H-bonding ability observed in chloroform is lost in water: all bases either organic or inorganic give the same result that is simply depending on concentration. A 0.1 molar ratio of base to nucleophile gives the best conversion, whereas addition of one equivalent of base or strong acid prevents the reaction from occurring. These results fit into a reaction sequence in which reversible addition to a dipolarophile is followed by acid-catalysed irreversible dehydration of the cycloadduct. This is a remarkable example of a condensation reaction occurring in water because of irreversible acid-catalysed water elimination. The reaction has been successfully applied to dipolarophiles containing a wide variety of functional groups, including carboxylic acids and ammonium salts, under mild conditions. This new click-style reaction is expected to be compatible with biological environments.Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.