Hydroxamic acid esters lactones

Lactones, which may be regarded as cyclic or inner esters, react similarly. Anhydrides of carboxylic acids also react with hydroxylamine to form hydroxamic acids ... 

As in 10-55 hydrazides and hydroxamic acids can be prepared from carboxylic esters, with hydrazine and hydroxylamine, respectively. Both hydrazine and hydroxylamine react more rapidly than ammonia or primary amines (the alpha effect, p. 445). Imidates, RC(=NH)OR, give amidines, RC(=NH)NH2. Lactones, when treated with ammonia or primary amines, give lactams. Lactams are also produced from y- and 5-amino esters in an internal example of this reaction. 

When the compound for identification fails to respond to test 4 (aldehyde or ketone), the next class reactions to apply are the hydroxamic acid test and saponification, i.e., hydrolysis in alkaline solution. These are the class reactions for esters and anhydrides the rarely-encountered lactones react similarly. 

Classical reactions involving nucleophiles such as saponification ("OH as the nucleophile), aminolysis (with amines also ammonia in ammonolysis reactions), transesterification (alkoxides, "OR) and others (hydrazinolysis, hydroxamic acid synthesis, etc.) have been adapted to solid phane and used to obtain, for instance, carboxylic acids, amides and esters. Internal or intramolecular nucleophilic attack has been employed to obtain cyclic products such as lactones, lactams (including cyclic peptides) and a great variety of heterocycles (hydantoins, diketopiperazines, benzodiazepinones, etc.). 

Peptide antibiotics. Antibiotics with linear or cyclic oligopeptide structures containing not only L- amino acids but often also unusual, non-proteinogenic amino acids. Homopeptides are built up exclusively of amino acids (e.g., gramicidins), the so-called heteropeptides also contain other structural elements, e.g., hydroxamic acids. Macrocyclic Ra. containing one or more ester bonds in the ring are known as peptide lactones (e.g., hormaomycin) or depsipeptides (e.g., valinomycin). 

The acid components can be detected as hydroxamic acids by reacting esters and lactones with hydroxylaniine. It must be tested whether these hydroxamic acids can be separated by TLC. 

Lactones will give a positive ester test, forming a hydroxamic acid when treated with alkaline hydroxylamine this acid gives an intense color with ferric chloride. This test has been used as a means of detecting lactones on a paper chromatogram (28). Free acids do not give it, and the paper must be treated with diazomethane first in order to convert the acids present to the esters. This method has also been used for the quantitative determination of gluconic 6-lactone (28a). 

Chromatographic analysis of a solution of an aldonic acid revecds the presence of both acid and lactone if present, the latter being represented by the faster moving spot. Aldonic acids, amides, lactones and esters can be detected on a paper chromatogram in the form of their hydroxamic acid derivatives . 

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