Hydroxamic acid derivatives anhydrides

If the acid chloride prepared as in Schemes 10.35 and 10.36 is treated with hydroxylamine hydrochloride in pyridine solution, the corresponding hydroxamic acid is generated. When the hydroxamic acid (Scheme 10.37) is allowed to react with acetic anhydride, the O-acetate results and, on heating, the hydroxamic acid derivative undergoes decomposition (the Lessen rearrangement) to produce the same A -substituted isocyanate as previously seen. 

The use of dehydrating agents such as sulfuric or phosphoric acid on (555 X = OH) was also successful, and these closures may proceed via mixed anhydrides 67AHC(8)277, 75MIP41600). Carbonyldiimidazole effected the conversion of hydroxamic acid (557) into a 3-hydroxy-1,2-benzisoxazole derivative (79JHC1277). The mixed anhydride (558) where... 

The simpler examples are readily hydrolysed in aqueous solution, and therefore react with sodium hydrogen carbonate and also give the ester test they may be confirmed by applying the hydroxamic ester test (Section 9.5.3, p. 1222). Carbonyl adsorption is apparent in the infrared spectrum at about 1820 cm-1 and at about 1760cm-1. It should be noted that aromatic anhydrides and higher aliphatic anhydrides are not readily hydrolysed with water and are therefore effectively neutral (Section 9.5.3, p. 1218). The final characterisation of the acid anhydride is achieved by conversion into a crystalline carboxylic acid derivative as for add halides. 

Aziridinones (z-lactums).3 The hydroxamic acid (1) is converted in almost quantitative yield to the a-lactam 2 when treated with triflic anhydride and triethylamine in CH2C12 at — 70°. This cyclization of a hydroxamic acid was first encountered in a thebaine derivative. 

The 1,4-dinucleophilic building blocks used most are 1,2-disubstituted ethanes of the type HXCHiCHjYH, semicarbazides, thiosemicarbazides, hydroxamic acid amides, amidrazones, and 1,2-disubstituted aromatic and heteroaromatic compounds. 1,1-Dielectrophilic building blocks preferentially used are perfluorinated carboxylic acids and their derivatives, such as acid halides, anhydrides, imidoesters, nitriles, perfluoroalkyl chlorosul-... 

The formation of hydroxamic acids is essentially irreversible and pulls the reaction to completion. ATP and similar phosphate compounds do not react with NH2OH. Reaction with hydroxylamine has long been used to determine acid derivatives such as esters, since hydroxamic acids form intensely colored complexes with ferric iron in acid solution. Acid anhydrides react much more readily than most other derivatives, and the hydroxamic reaction was introduced into biochemistry by Lipmann as a means for detecting acyl phosphate. Thioesters also react readily with... 

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