Carboxylic esters, acylation with hydroxylamine

The cyclic phosphonate may be intercepted with hydroxylamine to yield the corresponding hydroxamate. Importantly, the rate of hydroxylaminolysis is approximately the same as ethanol loss, thus it appears that the cyclic phosphonate and not a precursor pentacovalent species is being trapped. Insofar as the analogy is appropriate, hydroxylamine is trapping an acyclic acyl phosphate in the above case, albeit at a rate faster than benzyl alcohol loss. It is also noteworthy that for both the phosphonate and phosphate esters there is no net transfer of oxygen from the carboxyl to phosphorus during the entire course of hydrolysis, i.e. loss of two moles of alcohol. 

Hydroxylamines and hydrazines can be acylated on insoluble supports using the same type of acylating agent as is used for the acylation of amines [146-149]. Because of their higher nucleophilicity, hydroxylamines or hydrazines can be acylated more readily than amines, and unreactive acylating agents such as carboxylic esters can sometimes be successfully employed (Table 13.10). Polystyrene-bound O-alkyl hydroxamic acids can be N-alkylated by treatment with reactive alkyl halides and bases such as DBU (Entry 5, Table 13.10). 

In an effort to establish the methodology for construction of active sites by site-directed functionalization, 2,6-diacetylpyridineketoxime was attached to CD-PEI. The site-directed functionalization of CD-PEI was carried out by acylation in 13-19%(v/v) DMSO with rert-butylphenyl ester 45 of a carboxylic acid containing 2,6-diacetylpyridine followed by conversion of the carbonyl groups to oximes by treatment with hydroxylamine, leading to the formation of 46. By acylation in DMSO of CD-PEI with the phenyl ester, instead of the terf-butylphenyl ester, an analogue of 46 was prepared by random functionalization. 

Acyl chlorides are rarely used to convert hydroxylamine into hydroxamic acids 607,608 it is more effective to acylate hydroxylamine with carboxylic esters. 

Acylation of nitrogen compounds by carboxylic esters. The action of carboxylic esters on ammonia or primary or secondary amines generally leads to carboxamides under relatively mild conditions, and the analogous treatment of carboxylic esters with hydrazine and hydroxylamine provides the most important methods of preparing simple carboxhydrazides and carbohydrox-amic acids. 

Hydroxylamine is acylated by carboxylic esters, giving hydroxamic acids. The reaction often occurs in a few hours at room temperature if the components are mixed in alcoholic solution, preferably with addition of an equivalent of an alkoxide. In the latter case the hydroxamic acids are obtained as salts, but are easily liberated therefrom. 

The chromatographic behavior of choline and its esters has been studied by Whittaker and Wijesundera (98-100). The esters were detected on the paper by treatment with alkaline hydroxylamine and then with ethereal ferric chloride which is specific for carboxylic esters and certain other acyl derivatives. The lower limit of sensitivity was 0.6-2 ftg. A table of the B/ values of choline and many of its esters with various solvents was given and it was observed that the same values were obtained whether the esters were developed alone or in a mixture. Increasing the water content of the solvent increased the B/ values but reduced separation. Solvents with ammonia tended to destroy the esters which are alkali labile. 

Shin, C., K. Nanjo, M. Kato, and J. Yoshimura a,P Unsaturated Carboxylic Acid Derivatives. IX. The Cyclization of a-(N-Acyl-hydroxyamino) Acid Esters with Ammonia or Hydroxylamine. Bull. Chem. Soc. Japan 48, 2584 (1975). 

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