Derivatives of hydroxamic acids

Despite the biological importance and rich chemistry of hydroxamic acids (HAs), their organometallic derivatives have received little attention so far. Fully silylated (trimethylsilyl and t-butyldimethylsilyl) derivatives which are promising for medicinal applications have a structure derived from that of the tautomeric hydroximic acid with an E/Z ratio depending on the nature of the acid. Aliphatic acids yield disilyl derivatives in an approximate E/Z ratio of 2:3; aromatic HAs produce solely Z isomer irrespective of the phenyl ring substituent, Silylation of aliphatic dihydroxamic acids proceeds independently on both ends if the two hydroxamic groups are separated by one methylene group at least, It was not possible to determine the E/Z ratio for oxalic and malonic acid derivatives, It is shown that Si-29 and N-15 NMR chemical shifts are useful for differentiation between hydroximic and hydroxamic structures, but for determination of E and Z configurations spin-spin coupling must he used until more data relating Si-29, C-13 and N-15 chemical shifts tol the configuration are available for this class of compounds. The dependence of chemical shifts on Hammett substituent constants in ring-substituted benzhydroxamic acids is discussed, Some errors found in the literature on hydroxamic acids are also explained, Copyright (C) 2000 John Wiley & Sons, Ltd.