Structure determination of dihydroxamic acids and their trimethylsilyl derivatives by NMR spectroscopy

Abstract

Homologous series of dihydroxamic acids [HONHCO(CH 2 n CONHOH with n D 0, 1, 2, 3, 4 and 6] were prepared and trimethysilylated [1(n) and 2(n)]. The solution NMR spectra ( 1 H, 13 C, 15 N) of 1(n) show that the hydroxamic end groups assume Z-Z and Z-E combinations of conformers. An exception is oxalodihydroxamic acid, which assumes only one combination. 13 C cross-polarization magic angle spinning reproduces the solution chemical shift in this compound and indicates the Z-Z combination as determined earlier by x-ray diffraction. The trimethylsilylation produces compounds with a hydroximic structure on both ends, both groups being disilylated. Z-Z, Z-E and E-E isomer combinations are visible in the spectra and their ratio can be determined. Again, oxalodihydroximic acid derivatives are an exception: only one silylated product was found and its geometry could not be determined. Selective decoupling experiments ( 15 Nf 1 Hg and 13 Cf 1 Hg) are an inexpensive alternative to 15 N enrichment used to identify E and Z conformers. To differentiate hydroxamic and hydroximic structures, the most reliable parameter is the 15 N chemical shift, which differs in the two classes of compounds by about 120 ppm. To differentiate E and Z hydroxamic conformers 13 C chemical shifts of C O groups are preferable to 15 N chemical shifts but for distinguishing E and Z isomers of the hydroximic structure both 15 N and 13 C NMR of the C N group are useful. 17 O NMR data are of no practical value in this respect.

Kinetic and thermodynamic characterization of C–N bond rotation by N‐methylacetohydroxamic acid in aqueous media

“…Amides and HAs favor conformations that permit resonance stabilization . For HAs, the conformations have been labeled E and Z based on the relative placement of oxygen atoms and on the partial double bond character resulting from resonance stabilization . Figure shows E and Z conformations of a small secondary HA, N ‐methylacetohydroxamic acid (NMHA) that is the subject of the current study.…”

Conformational analysis of a secondary hydroxamic acid in aqueous solution by NOE spectroscopy

“…The hydroxamic acid is a naturally occurring metal ligand with high affinity for ferric iron. The relevance of hydroxamic acids to medicine, microbial iron harvesting, and industrial metal‐binding applications has prompted the development of various model systems . Hydroxamic acids favor two conformations, the so‐called E and Z (antiperiplanar and synperiplanar; Fig.…”

“…Hydroxamic acids favor two conformations, the so‐called E and Z (antiperiplanar and synperiplanar; Fig. ) . The hydroxamate unit must exist in the Z conformation in order to function as a bidentate metal ligand.…”

“…Assignment of E and Z forms has been made most frequently using NMR chemical shift trends . The propensity for hydroxamic acids to aggregate in nonpolar media selectively stabilizes the Z form at higher concentrations, which has been used as a basis for assignment [4b,7,9] .…”

“…The relevance of hydroxamic acids to medicine, microbial iron harvesting, and industrial metal-binding applications has prompted the development of various model systems. [1][2][3][4][5][6][7][8][9][10][11][12][13] Hydroxamic acids favor two conformations, the so-called E and Z (antiperiplanar and synperiplanar; Fig. 1).…”