Hydroxamate ion

The enhanced reactivity of hydroxamate ions is in general applicable to base-catalyzed reactions. For example, base-catalyzed proton-abstraction from or-ketols (11) is efficiently promoted by combinations of hydroxamate + CTAB micelle or hydroxamate + cationic polysoap (Shinkai and Kunitake, 1976c, 1977d). The rate acceleration amounts to 3000-20 000-fold, and the rate... 

Free energy variations with temperature can also be used to estimate reaction enthalpies. However, few studies devoted to the temperature dependence of adsorption phenomena have been published. In one such study of potassium octyl hydroxamate adsorption on barite, calcite and bastnaesite, it was observed that adsorption increased markedly with temperature, which suggested the enthalpies were endothermic (26). The resulting large positive entropies were attributed to loosening of ordered water structure, both at the mineral surface and in the solvent surrounding octyl hydroxamate ions during the adsorption process, as well as hydrophobic chain association effects. 

Quantitatively, the enhanced reactivity of hydroxylamine, as well as oximate and hydroxamate ions and also other a-nucleophiles, is expressed as a positive deviation on a Br0nsted-type rate-basicity (pX a) ploh i-e. log k vs pTsTa - This is illustrated in Figure 1 for oxygen nucleophiles and in Figure 2 for nitrogen nucleophiles. It is important to note that the reactivity of the a-nucleophile is considered relative to a normal nucleophile of the same Brpnsted basicity. ... 

The most common deviation is the exceptionally high reactivity of nucleophiles, such as hydroperoxide, hypochlorite and hydroxamate ions, with atoms bearing lone-pair electrons next to the nucleophilic centre. This phenomenon, known as the alpha-effect287, is found for aminolysis reactions of esters also285, and is commonly observed for attack at electrophilic centres where reactivity depends fairly strongly on the basicity of the nucleophile. Negative deviations may be evidence of steric hindrance, or in a few cases, in particular that of hydroxide ion, may reflect special solvation effects on the pKa or the nucleophilicity (or both) of the nucleophile. 

Kinetic studies of the reaction at pH 7.7 of 4-nitrophenyl acetate with three hydroxa-mates, RCONHO- (R = Me, Ph, 2-HOC6H4) in various water-solvent (DMSO, DMF, MeCN, and 1,4-dioxane) mixtures have shown that these a-effect nucleophiles react faster with increasing percentages of DMF and DMSO, but not with MeCN and 1,4-dioxane. The likely explanation is desolvation of the hydroxamate ions by the highly polar solvents, DMF and DMSO.13... 

Singh N, Karpichev Y, Shartna R, et al. From a-nucleophUes to functionalized aggregates exploring the reactivity of hydroxamate ion towards esterolytic reactions in micelles. Org Biomol Chem. 2015 13 2827-2848. 

This reaction, conducted in alkaline solution, also produces carboxyl groups by hydrolysis of the amide (54). Recent work on the reaction of polyacrylamide with hydroxylamine indicates that maximum conversion to the hydroxamate fiinctionahty (—CONHOH) takes place at a pH > 12 (57). Apparendy, this reaction of hydroxylamine at high pH, where it is a free base, is faster than the hydrolysis of the amide by hydroxide ion. Previous studies on the reaction of hydroxylamine with low molecular weight amides indicated that a pH about 6.5 was optimum (55). 

When Jencks reacted hydroxylamine with p-nitrophenyl acetate, p-nitrophenolate ion was released at a rate faster than that at which acetohydroxamic acid was formed. This burst effect is evidence for a two-step reaction. In this case the intermediate is O-acetylhydroxylamine, which subsequently reacts with hydroxylamine to form the hydroxamic acid. 

In three of the compounds (154, R2= H) examined the commonest loss from the molecular ion was the cyanide RjCN to give the most predominant ion at m/e= 120 in each case. The M-0 peak (M-16), was observed in cyclic hydroxamic acids (154, R = OH). 

This alkyl migration is believed to proceed via ion-pair formation. These and many other simple 0-alkyIated cyclic hydroxamic acids are thermally stablebelow 180°. 

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. 

Iron transport agents may belong to the protein or non-protein class. In the former group are found the animal proteins transferrin (25), lactoferrin (26) and conalbumin (27). The low molecular weight iron carrying compounds from microorganisms, the siderochromes, may occur with or without a bound metal ion. Typically, severe repression of biosynthesis of these substances can be expected to set in at an iron concentration of ca. 2 x 10-5 g atoms/liter (28). Most, but not all, of these substances can be described as phenolates or hydroxamates (4). 

Metal alkoxides undergo alkoxide exchange with alcoholic compounds such as alcohols, hydro-xamic acids, and alkyl hydroperoxides. Alkyl hydroperoxides themselves do not epoxidize olefins. However, hydroperoxides coordinated to a metal ion are activated by coordination of the distal oxygen (O2) and undergo epoxidation (Scheme 1). When the olefin is an allylic alcohol, both hydroperoxide and olefin are coordinated to the metal ion and the epoxidation occurs swiftly in an intramolecular manner.22 Thus, the epoxidation of an allylic alcohol proceeds selectively in the presence of an isolated olefin.23,24 In this metal-mediated epoxidation of allylic alcohols, some alkoxide(s) (—OR) do not participate in the epoxidation. Therefore, if such bystander alkoxide(s) are replaced with optically active ones, the epoxidation is expected to be enantioselective. Indeed, Yamada et al.25 and Sharp less et al.26 independently reported the epoxidation of allylic alcohols using Mo02(acac)2 modified with V-methyl-ephedrine and VO (acac)2 modified with an optically active hydroxamic acid as the catalyst, respectively, albeit with modest enantioselectivity. 

Vanadium-catalyzed asymmetric epoxidation has recently been re-examined with a newly designed chiral hydroxamic acid (3).43-45 The hydroxamic acid (3) forms a 1 1 complex with vanadium ions and induces high enantioselectivity (Scheme 6). 

Fe(III) displacement of Al(III), Ga(III), or In(III) from their respective complexes with these tripodal ligands, have been determined. The M(III)-by-Fe(III) displacement processes are controlled by the ease of dissociation of Al(III), Ga(III), or In(III) Fe(III) may in turn be displaced from these complexes by edta (removal from the two non-equivalent sites gives rise to an appropriate kinetic pattern) (343). Kinetics and mechanism of a catalytic chloride ion effect on the dissociation of model siderophore-hydroxamate iron(III) complexes chloride and, to lesser extents, bromide and nitrate, catalyze ligand dissociation through transient coordination of the added anion to the iron (344). A catechol derivative of desferrioxamine has been found to remove iron from transferrin about 100 times faster than desferrioxamine itself it forms a significantly more stable product with Fe3+ (345). 

The ease of formation of hydrophobic ion pairs, and hence the rate acceleration, will be determined by the hydrophobic and electrostatic interactions between the anionic and cationic species. Lapinte and Viout (1974) found that the nucleophilic order OH- > CN > C6H50- in water was completely reversed in CTAB micelles hydrophobic phenoxide ion is activated better by the micelle. The micellar binding of phenols and phenoxides was determined by Bunton and Sepulveda (1979). Similarly, hydrophobic hydroxamates are activated much better than their hydrophilic counterparts. In the same vein, the extent of activation correlates approximately with the hydrophobic nature of aqueous aggregates as estimated by Amax of methyl orange (Table 7) and of picrate ion (Bougoin et al., 1975 Shinkai et al., 1978f Table 5). 

As an extension of the research on hydrophobic ion pairs, ion pairs such as tetraethylammonium hydroxamate [63] have been prepared and their nucleophilic reactivity estimated in organic solvents (Shinkai and Kunitake, 1976d Shinkai et al., 1979a). The ion pair showed very high nucleophilicity toward... 

As mentioned repeatedly, a variety of anionic reagents are highly activated in the hydrophobic microenvironment of cationic micelles and polysoaps. The range of anionic reagents studied in the past includes imidazole, hydroxide, thiolates, oximates, hydroxamates, carboxylates and carbanions. Polyanionic coenzymes are similarly activated. These results can be interpreted in a unified way by the concept of hydrophobic ion pairs, and the major source of activation seems to be concentration and desolvation of the anionic reagent in the... 

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