posted on 2003-11-28, 00:00authored byNathaniel C. Lim, Martha D. Morton, Hilary A. Jenkins, Christian Brückner
The synthesis of squaric acid N-hydroxylamide esters 5 and amides 6 from dimethyl squarate 2a
is described. These derivatives are analogues of the naturally occurring iron(III) chelator hydroxamic
acid. On the basis of a comparative reactivity study, a concerted retro-Cope mechanism for the
formation of the N-hydroxylamide esters 5 by reaction of dimethyl squarate with hydroxylamines
is proposed. A preliminary iron(III) binding study of these hydroxamic acid analogues is presented,
demonstrating binding of iron(III) to amides 6 in aqueous solutions, while the esters 5 did not
show any sign of metal ion binding. 13C NMR spectroscopic data (chemical shift and spin−lattice
relaxation time determination) of these and related derivatives delineate the resonance structures
predominant in these molecules. The resonance structures of the derivatives rationalize their
spectroscopic data, chemical reactivity, and iron(III) binding properties. Single-crystal X-ray
structure analyses of squaric acid N-hydroxylamide ester 5b and squaric acid N-hydroxylamide
amide 6c confirm their connectivity and provide structural evidence supporting the spectroscopically
derived conclusions. The squaric acid N-hydroxylamides are potentially useful in the construction
of chemosensors for iron(III).