A synthetic strategy for previously unknown para-substituted N,NЈ-dihydroxybenzamidines and their O-monosubstituted and O,OЈ-disubstituted methyl, benzyl, and tetrahydropyranyl derivatives is described. The procedure starts with the corresponding hydroxamic acid chlorides, which after dehydrohalogenation give nitrile oxides. These intermediates in turn react with O-substituted hydroxylamines to afford the desired N,NЈ-dihydroxybenzamidines after workup. This new class of potential prodrugs was characterized by [a]

A synthetic strategy for previously unknown para‐substituted N,N′‐dihydroxybenzamidines and their O‐monosubstituted and O,O′‐disubstituted methyl, benzyl, and tetrahydropyranyl derivatives is described. The procedure starts with the corresponding hydroxamic acid chlorides, which after dehydrohalogenation give nitrile oxides. These intermediates in turn react with O‐substituted hydroxylamines to afford the desired N,N′‐dihydroxybenzamidines after workup. This new class of potential prodrugs was characterized by 15N NMR spectroscopy. The chemical shifts show significant correlations with Hammett σ values, especially for the oxime‐type nitrogen with r2 > 0.99. The Hammett σ parameter reliably correlates with electron density in molecules. The presented results thus allow predictions relating to π‐electron density and basicity in this functional group, and these are important parameters for the discussion of substrate enzyme interactions.

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Synthesis of p-Amino-N,N'-dihydroxybenzamidine Using a TBDMS Protecting Group Protocol. -A simple protocol is presented for the reaction of hydroxamic acid chlorides (I) with hydroxylamine (II). The resulting amidine (IIIc) is further converted into the title compound (V) via nitro reduction and O-deprotection. -(SCHWARZ, L.; GIRRESER, U.; CLEMENT*, B.; Tetrahedron Lett. 55 (2014) 22, 3322-3324, http://dx.

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