HYDROXAMIC ACIDS AND THEIR DERIVATIVES

TR Govindachari, S Rajappa, AS Akerkar, VS Iyer. Hydroxamic acids and their derivatives IV. Further studies on the use of esters of pivalohydroxamic acid for peptide synthesis. Tetrahedron 23, 4811, 1967. 

The reaction of dicyano epoxides 105 with hydroxylamines hydrochlorides 106 in acetonitrile represents a direct route via 107 to a number of new and higher a-chloro hydroxamic acids and their derivatives 108 (Scheme 55) . ... 

Alkali salts of hydroxamic acids and their derivatives undergo a re> arrangement to give isocyanates. The method has had little synthetic application it has been reviewed. ... 

There has as yet been no systematic work on the mass spectra of cyclic hydroxamic acids, but from the limited information available the direct loss of 0 or OH from the molecular ion is to be expected. The fragmentation behavior of the 0-alkyl derivatives is rather unpredictable, although again processes involving fission of the N—0 bond are generally important. Table II shows the prominent first-generation fragment ions from a few hydroxamic acids and their ethers. 

Complexation of metal ions by hydroxamic acids is the starting point of a number of analytical determinations . All hydroxamic acids, in acid solutions, react with ferric chloride to give rust brown complex salts 89 (Scheme 47). These colored complexes form the basis for the sensitive qualitative and quantitative determination of carboxylic acids and their derivatives too. 

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 lactim/lactam tautomerism of hydroxamic acids and their O-alkyl and O-acyl derivatives has also been studied [146], Hydroxamic acids exist in the solid state and in polar solvents as the lactam tautomer only, whereas in nonpolar solvents the hydroximic tautomer is also present. Further analogous solvent-dependent lactim/lactam equilibria have been observed for certain Schiff bases (prepared from anilines and 2(4)-hydroxybenzaldehyde [256] or 2-hydroxynaphthaldehyde [257]), for 3-hydroxypyrazole [258], and for 3-methyl-l-phenylpyrazolin-5-one [259]. 

Hydroxamic acids and their amino acid derivatives formed a series of dioxomolybdenum(VI) complexes of the type cis-[Mo02(hdx)2] and [Mo02(hdxamc)2] (hdxH, (10) hdxamcH, (11)), which are attractive as models for siderophores and for the development of metal-chelating drugs. 

Hydro xamic Acids and Esters The photodissociation of hydroxamic acids and ester derivatives (10.34) was reported for a long time, although their photochemistry remains unclear [67-69]. The decomposition of dibenzoylhydroxylamines is considered as occurring through a N-O bond cleavage photopolymerization of methylmethacrylate was reported to be effective. 

DFP is stable and in the absence of moisture can be stored for considerable periods without decomposition. Hydrolysis in neutral aqueous solution occurs slowly. The reaction is catalyzed by both acid and base. At pH>7, hydrolysis is proportional to the hydroxide ion concentration and at high pH is extremely rapid. The product is always diisopropyl phosphoric acid (equation 38), except under more forcing conditions which eventually produce phosphate (and propan-2-ol). The hydrolysis is strongly catalyzed by the addition of a-effect nucleophiles such as hypochlorite, peroxide, hydroxylamine, hydroxamic acid and their substituted derivatives . Under basic conditions, such nucleophiles (HOX) are present as the anion and are responsible for the rapid initial displacement of fluoride ion from DFP to give intermediate 36 shown in equation 39. Displacement of OX by hydroxide ion regenerates the catalytic OX anion. The reaction with hydrogen... 

The conversion of carboxylic acids and their derivatives into isoQranates is a synthetically useful and well-known transformation and two new methods now add to the available methodology. In one, amides are transformed electrochemically imder mild conditions to isocyanates, which are isolated or trapped as the corresponding carbonates. In the other method, adducts of nitrosocarbonylbenzenes (generated by oxidation of hydroxamic acids) and 9,10-dimethylanthracene are decomposed in benzene at 80 °C in the presence of triphenylphosphine, to give aryl isocyanates in high yield. ... 

The chemistry of 1,4-(oxa/thia)-2-azoles, was founded in the late 1930s, when Musante first correctly suggested the 5-imino-2-phenyl 1,4,2-oxathiazole structure (1) for the product obtained from the reaction of ammonium thiocyanate and benzhydroximoyl chloride <38G33l>. Later, Beck described the preparation of dioxazolones (2) and some of their properties <51CB688>, while the first nonconjugated dioxazole derivative (3) was prepared by Exner from hydroxamic acid and benzophenone diethylacetal <56CLY779>. 

Petho, M. 1992. Occurrence and physiological role of benzoxazinones and their derivatives. IV. Isolation of hydroxamic acids from wheat and rye root ssecretions. Plant Physiol. Agrochem. 41, 167-175... 

Most of the naturally-occurring pyrazine hydroxamic acids appear to be derived from valine, leucine and isoleucine, and biosynthetic studies by MacDonald and coworkers (61JBC(236)512, 62JBC(237)1977, 65JBC(240)1692) indicate that these amino acids are incorporated. However, it would seem that the logical intermediates, viz. the 2,5-dioxopiperazines such as (111) and (112), are not always incorporated. This does not rule out their intermediacy, as there may be problems such as low solubility or membrane permeability which prevent their efficient incorporation. An exception to these results was reported for pulcherrimic acid (113) (65BJ(96)533), which has been shown to be derived from cyclo-L-leu-L-leu which serves as an efficient precursor. 

The following discussion of hydroxamic acids includes saturated systems, e.g., 2, compounds such as 3, derived from aromatic systems, 7V-hydroxyimides such as 7V-hydroxyglutarimide (78), and certain of their derivatives including thiohydroxamic acids. Naturally occurring cyclic hydroxamic acids are discussed to show the range of structural types that has been found, hut macrocyclic polyhydroxamic acids are mentioned very briefly, because several comprehensive reviews of these compounds are already available. The main purpose of this review is to summarize the methods available for the synthesis of cyclic hydroxamic acids, to outline their characteristic reactions, and to present some useful physical data. Their synthesis and some biological properties have previously been reviewed by Coutts. ... 

The more activated the ester, the less stable is the compound. All the esters mentioned above can be used as shelf-stable reagents except benzotriazolyl esters, which decompose too readily. In addition to their use as activated forms of the A - a I ko x y ca r bo n y I am i n o acids, the esters derived from hydroxamic acids are implicated as intermediates in coupling reactions in which the A-hydroxy compounds have been added to promote efficient coupling between an acid and a primary or secondary amine (see Section 2.10). It is pertinent to mention that the O-acylisourea generated from carbodiimides (see Section 2.02) is an activated ester but one of nature different than those alluded to above. 

The intimate relationship between NMR parameters such as chemical shifts and spin-spin coupling constants and molecular geometry is particularly evident for derivatives with rigid frameworks. Therefore, structural and conformational effects are treated first as a separate topic and then in conjunction with specific compounds. As data on hydroxylamines, oximes and hydroxamic acids are not as extensive as those for other types of systems containing nitrogen or oxygen, comparisons with their respective parameters or effects have also been included wherever they are considered relevant. 

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