Hydroxamic acids acid imides

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. 

FIGURE 2.11 Structures and nomenclature of compounds that serve as auxiliary nucleophiles. Generation of activated esters. Substituted hydroxamic acids are sometimes added to carbodi-imides or other reactions to improve the efficiency of couplings. The additive suppresses side reactions by converting activated species into activated esters (see Section 2.10) before they have time to undergo secondary reactions, p(Me2SO) HOBt 9.30, HOAt 8.70. 

Amides, Imides, Hydrazides, Hydroxamic Acids, and Azides... 

The use of the term ester-like is deliberate, as it is known that hydroxylamine will react with many other groupings to form hydroxamic acids. Among these are imides, anhydrides, acid chlorides, amides, and certain peptide linkages (Yale, 1943 Gallop el al., 1959 Williams et al.,... 

Electrophilic N-aminations have been performed with hydroxylamine-O-sulfonic acid (HOSA)," O-(2,4-dinitrophenyl)hydroxylamine and C>-mesitylenesulfonylhydroxylamine. The use of HOSA is mainly restricted to aqueous reaction media. Imide sodium salts of some heterocycles such as theobromine (88) can be converted to hydrazine derivatives by treatment with 0-(diphenylphosphinyl)hydroxylamine (equation 35)." This reaction has been extended to synthesis of N-arylhyd ines, where R and R are hydrogen, alkyl or aryl (equation 36)." Similarly, trisubstituted hydrazines can be prepared by the use of N-aryl-O-acetylhy oxylamines and secondary amines." A recent publication" concerning the synthesis of l-acyl-2-dkylhydrazines from hydroxamic acids and amines in the presence of activating agents has been found to be erroneous no N—N bond formation occurs under these conditions." ... 

The reaction is neither specific nor selective, since many carboxylic acids, acid anhydrides, acid halides, acid amides and imides, trihalo compounds, and even lactones give the same reaction. Also many nitrogen-bearing compounds give a positive reaction. Some references suggest that a blank be prepared in whi the substance to be examined is treated as described, but without converting it into a hydroxamic acid, because some substances give a color reaction alone. ... 

Other imides that mimic more closely the penicillins were synthesised [176] (Scheme 102). The good acylating power of 329 and 330 was demonstrated by their very fast reaction with hydroxylamine to give hydroxamic acids. Com-... 

TABLE XI-33. Pyridine Side-Chain Hydrazides, Hydroxamic Acids, Amidines, and Imides (Continued)... 

Bis(trimethylsilyl)acetamide. Bis(trimethylsilyl)acetamide (BSA) has been formulated as iV,iV-bis(trimethylsilyl)acetamide as well as the imidate form. The NMR spectra of a number of silylamide derivatives ( C, Si, and 0) have been investigated. Whereas BSA is seen to exist in the imidate form, some analogs, for example bis(trimethylsilyl)formamide, exist in the IVW-bis(trimethylsilyl) form, and the product obtained by the interaction of l,2-bis(chlorodimethylsilyl)ethane with BSA is also clearly in the alternative foim Trimethylsilyl derivatives of hydroxamic acids are formed in reactions using hexamethyl-disilazane and are similar in structure to BSA. This entry will concentrate on examples from the more recent literature. 

Amidation. A number of other various amidation reactions have been conducted using BOP. Such preparations include A) O-dimethyl hydroxamates of amino acids and peptides (precursors of chiral peptidyl aldehydes), heterocyclic amide fragments in the synthesis of macrolide and porphyrin models, dan-sylglycine anhydride as a mixed sulfonic-carboxylic imide by dehydration-cyclization of dansylglycine, and selective monoacylation of heterocyclic diamine in carbohydrate series (eq 9). ... 

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