Direct synthesis of furan-2,5-dicarboxylic acid monoamides

A regioselective monoamidation of furan-2,5-dicarboxylic acid using O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate is presented. The excellent regioselectivity in favour of activated monobenzotriazoyl ester as a intermediate is achieved by gradual addition of a coupling reagent into a dilute solution of furan-2,5-dicarboxylic acid and N,N-diisopropylethylamine in dimethylformamide. Divided crude reaction mixture is used directly in the subsequent coupling reactions with benzylamine, diethylamine, piperidine and aniline, respectively. Four representative monoamides are prepared and isolated in very good yields 73-82%. Traces of symmetric diamides were also detected, however never in isolable amounts.