Hydroxamic acids amides

The imidazo[5,l -e]-l.2,3,5-Letrazine-8-carbonyl chloride 17 reacts preferentially with nucleophiles (Nu ) at the 8-carbonyl group rather then at the 4-oxo group, allowing the preparation of a wide range of ester, thioester, amide, hydroxamic acid, hydrazide, sulfoximide, azide, and diazoacetyl derivatives.42... 

Conversions of compounds 116, 120 and 123 into IP-2-ones described above belong to Hofmann-, Curtius- and Lossen-type reactions. Therefore the parent amides, hydroxamic acids and o-aminopyridinecarboxylic acid azides, may formally be regarded as derivatives of monoaminopyridines. The above compounds rearrange into o-diamines with various degrees of ease, while benzenesulphonate 121 is transformed into intermediate isocyanate 122 under extremely mild conditions (68JOC2543). 

Hydroxamic acid formation resembles amide formation (pp. 117-119) and therefore certain other classes of substances will respond to the test, e.g., acid chlorides and acid anhydrides, but these substances are readily distinguished by other reactions. 

It may be noted that primary aliphatic amides are readily converted by hydro-xylamlne hydrochloride into hydroxamic acids, which may be detected by the addition of ferric chloride solution ... 

Acyl derivatives, RCO—NH—OH and HjN—O—CO—R, are named as A-hydroxy derivatives of amides and as O-acylhydroxylamines, respectively. The former may also be named as hydroxamic acids. Examples are A-hydroxyacetamide for CH3CO—NH—OH and O-acetylhydrox-ylamine for HjN—O—CO—CH3. Further substituents are denoted by prefixes with O- and/or A-locants. For example, C5H5NH—O—C2H5 would be O-ethyl-A-phenylhydroxylamine or A-ethox-ylaniline. 

The hydrogenolysis of hydroxamic acids (22) and hydra2ides (23) has also been used to synthesi2e amides. One of the earliest methods for the preparation of amides consists of treating acid chlorides with dry ammonia or an amine (24). 

If primary or secondary amines are used, A/-substituted amides are formed. This reaction is called aminolysis. Hydra2ines yield the corresponding hydra2ides, which can then be treated with nitrous acid to form the a2ides used in the Curtius rearrangement. Hydroxylamines give hydroxamic acids. 

No simple pteridine 1- or 3-oxides are yet known. If the AT-atom of an amide function is formally oxidized, tautomerism favours the cyclic hydroxamic acid structure, as found for 3-hydroxypteridin-4-one (55JA3927), 1-hydroxylumazine (64JOC408) and 2,4-diamino-8-hydroxypteridin-7-ones (75JOC2332). 

Me3Si)2NH, Me3SiCl, Pyr, 20°, 5 min, 100% yield. ROH is a carbohydrate. Hexamethyldisilazane (HMDS) is one of the most common sily-lating agents and readily silylates alcohols, acids, amines, thiols, phenols, hydroxamic acids, amides, thioamides, sulfonamides, phosphoric amides, phosphites, hydrazines, and enolizable ketones. It works best in the presence of a catalyst such as X-NH-Y, where at least one of the group X or Y is electron-withdrawing. ... 

Shaw and McDowellhave prepared imidazolone derivatives by cyclization of a-acylamino amides. In a variation of this reaction the azlactone (30) was gradually converted to the hydroxamic acid (31) by methanolic hydroxylamine. Sodium methoxide and hydroxylamine readily gave the acyclic hydroxamic acid (32) which could be cyclized to 31 by dilute acid. Benzyloxyurea has been used in the sjrnthesis of pyrimidine hydroxamic acids (33) by reaction with /S-diketones followed by catalytic hydrogenation of the benzyl group. Protection... 

Because of their higher oxidation level with respect to both amides and nitrones, hydroxamic acids have been sought from either by oxidative processes. 

Direct amidation can be carried out if an aromatic compound is heated with a hydroxamic acid in polyphosphoric acid, though the scope is essentially limited to phenolic ethers. 

Amidation of aromatic rings with hydroxamic acids... 

Knobler Y, Bittner S, Frankel M (1964) Reaction of N-carboxy-alpha-amino-acid anhydrides with hydrochlorides of hydroxylamine O-alkylhydroxylamines + amines syntheses of amino-hydroxamic acids amido-oxy-peptides + alpha-amino-acid amides. J Chem Soc 3941... 

As early as 1899, 8tieglitz proposed a tetrahedral intermediate for the hydrolysis of an imino ether to an amide. Thns it was clear qnite early that a complicated overall transformation, imino ether to amide, would make more sense as the result of a series of simple steps. The detailed mechanism proposed, althongh reasonable in terms of what was known and believed at the time, wonld no longer be accepted, but the idea of tetrahedral intermediates was clearly in the air. 8tieglitz stated of the aminolysis of an ester that it is now commonly snpposed that the reaction takes place with the formation of an intermediate prodnct as follows referring to work of Lossen. (Note that the favored tautomer of a hydroxamic acid was as yet unknown.)... 

Much more important than these reactions, however, are the reactions of CDI and its analogues with carboxylic acids, leading to AAacylazoles, from which (by acyl transfer) esters, amides, peptides, hydrazides, hydroxamic acids, as well as anhydrides and various C-acylation products may be obtained. The potential of these and other reactions will be shown in the following chapters. In most of these reactions it is not necessary to isolate the intermediate AAacylazoles. Instead, in the normal procedure the appropriate nucleophile reactant (an alcohol in the ester synthesis, or an amino acid in the peptide synthesis) is added to a solution of an AAacylimidazole, formed by reaction of a carboxylic acid with CDI. Thus, CDI and its analogues offer an especially convenient vehicle for activation of... 

Polymer-bound 1-hydroxybenzotriazole 1008 reacts with carboxylic acids in the presence of 1,3-diisopropylcarbo-diimide (1,3-DIC) and DMAP to produce esters 1009. Treated with hydroxylamine, esters 1009 are converted to hydroxamic acids 1010 (Scheme 167) <20030BC850>. Starting 1-hydroxybenzotriazole 1008 is recycled in the process and can be used for other syntheses. This method is well suited for automated synthesis of a library of hydroxamic acids. In similar applications of polymer-supported 1-hydroxybenzotriazole 1008, a wide variety of amides is synthesized <1997JOC2594, 2002JC0576>. 

Scheme 3 outlines synthetic strategies for the introduction of a range of substituents on the amide, alkoxyl and acyloxyl side chains. Hydroxamic esters 23 are readily synthesised from potassium salts of hydroxamic acids 21 according to Cooley et al.7 8 9 or by condensation of the corresponding acid chloride 24 with an alkoxyamine. 

Aldehyde 54 and the hydroxamic acids 55 were generated together in an acid-catalysed elimination reaction (Scheme 7 pathway (ii)). A crossover experiment indicated that esters are formed in a concerted rearrangement concomitant with the likely formation of the hydroxynitrene 57 (Scheme 7 pathway (iii)) while there is no evidence to date for the formation of hydroxynitrene, joint solvolysis of equimolar quantities of /V-acetoxy-/V-butoxy-/>-chlorobenzamide 26e and N- acetoxy-/V-benzyloxybenzamide 27a afforded significant quantities of butyl p-chlorobenzo-ate (36%) and benzyl benzoate (54%) as the only esters. This is an example of a HERON reaction, which has been identified in these laboratories as a characteristic rearrangement of bisheteroatom-substituted amides.32,33,42 43 155 158 Since ester formation was shown to prevail in neutral or low acid concentrations, it could involve the conjugate anion of the hydroxamic acid (vide infra).158... 

Further work by the same group resulted in the identification of indole amides as an alternative capping group for aliphatic hydroxamic acids [31]. Starting from... 

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