Hydroxamic acid deprotonated

In the Lossen reaction a hydroxamic acid derivative (usually an 0-acyl derivative) is deprotonated by base, and rearranges via migration of the group R to give an isocyanate 2. Under the usual reaction conditions—i.e. aqueous alkaline solution—the isocyanate reacts further to yield the amine 3. The Lossen reaction is closely related to the Hofmann rearrangement and the Curtins reaction. 

Complexes with deprotonated hydroxamic acids, catechols, and related ligands 319... 

Since differences were often reported in product yields from photochemical and thermal reactions, it was not clear that the same intermediate was generated in both cases. This issue was complicated by the fact that the temperatures under whieh the two experiments were run were usually quite different. The acid-base chemistry of nitrenium ions was largely unexplored so it was not known under what conditions these species could be protonated or deprotonated. It had also not been demonstrated that nitrenium ions played any role in the biological activity of mutagenic and carcinogenic esters of N-arylhydroxylamines or hydroxamic acids, particularly in their reactions with the DNA bases. Over the next decade these issues would be resolved but many questions about nitrenium ion chemistry would remain unanswered. 

According to the Brpnsted definition, the acidity of a molecule is associated with its capacity to give up a proton Ph—NH2 — Ph—NH +H+. The change of standard enthalpy or free energy of this deprotonation reaction is a measure of the intrinsic acidity. As discussed above, in solution, the propensity of an aniline derivative is to accept a proton. The measured dissociation constant (pATa) is related to the basicity of the neutral molecule (or the acidity of the anilinium cations). As a consequence, relatively little is known about their acidity and/or the anilinide anions. However, the NH acidities have been well established in hydroxamic acids even though the latter usually behave as O-acids134. It is therefore of interest to get some insight into the deprotonation of aniline in the gas phase. 

Quenching is associated to the stepwise deprotonation of the three hydroxamic acid fragments of 8, whose pA A values range between 8.2 and 9.5. In particular, the... 

Di-(7-alkylation of the hydroxamic acids (128) with 1,2-dibromoethane furnishes the 1,4,2-dioxa-zines (12a) in good yield (Equation (29)) <90CC327,92LA997). Alkylation initially takes place on the hydroxyl group before a second deprotonation at the NH group induces alkylation on the carbonyl oxygen. 

Complexes widi deprotonated hydroxamic acids and related ligands... 

Zhang, Baker, and Pulay have developed an efficient pK estimation protocol based on DFT (OYLP/6-311+G ) calculations of the deprotonation energy AE along with the COSMO solvent model [172], They found that application of a reliable solvent model was crucial to the success of their approach, whereas the particular DFT functional employed and the basis set played more modest roles. These workers applied their procedure to a wide range of compound classes, including carboxylic acids, phos-phonic acids, phenols, alcohols, hydroxamic acids, oximes, and thiols, with impressive results [230]. 

A soln. of startg. hydroxamic acid in dichloromethane treated with a 20% molar excess of methyl triflate at room temp, for 48 h - intermediate nitrone hydrotriflate (Y 95%), in deuteriochloroform deprotonated with a 20% molar excess of triethylamine methyl N-(l,l-dimethylethyl)-benzenecarboximidate N-oxide (Y 85% overall). The products are relatively unstable, being converted to 1-functionalized nitrones with a variety of nucleophiles. F.e., also with ethyl triflate, and deprotonation on silica gel or with the weakly basic anion exchange resin. Bio-rad AG3-X4, s. J.A. Warshaw et al., J. Org. Chem. 54, 1736-43 (1989). 

Based on the existence of numerous hydroxamate-containing secondary metabolites such as mycelianamide, it can be further proposed that the tryptophyl oxidation proceeds through a hydroxamic acid intermediate (shown in Scheme 10). This functionality, an excellent chelator of (a non-heme) Fe(lll), for instance, could further function to assist the elimination of water to form the imino portion of the azadiene. Since the prolyl methine (pKa>30) must also be removed at the active site of an enzyme, a metal-coordinated amide might also be essential to lower the activation barrier for the deprotonation step. Finally, the intramolecular Diels-Alder cycloaddition might enjoy a catalytic effect of aza-diene-metal coordination. 

The Lossen rearrangement of hydroxamic acids has been reported to proceed by way of metal complexes of deprotonated hydroxamic acids (Scheme 171). ... 

Reactions in most functional micelles involve nucleophilic attack by an anionic moiety, e.g. oximate, hydroxamate, thiolate or alkoxide. Therefore it may be necessary to take into account the acid-base equilibrium which generates the anionic moiety. The simplest approach is to work at a pH such that deprotonation is essentially quantitative, but if this cannot be done the extent of deprotonation has to be measured directly or estimated. 

APCI has become a popular ionization source for applications of coupled HPLC-MS. Figure 1.33 shows an example of an application of HPLC-APCI coupling [79]. It shows the analysis obtained from extracts of maize plants. Six compounds are identified by mass spectrometry. These compounds have been identified as glucoconjugated DIMBOA (2,4-dihydroxy-7-methoxy-l,4-benzoxazin-3-one) and similar molecules that differ by the number of methoxy groups in the benzene ring and/or by the N-O methylation of the hydroxamate function. This example clearly shows the influence of the analyte on the type of observed molecular species. Indeed, the presence of an acidic group in the compound from peak 1 allows mainly the detection of deprotonated molecular ions, whereas the compound from peak 4 does not contain an acid group and thus leads only to the formation of adduct ions. 

Compound 82, containing a deprotonated bridging A-hydroxyglutarimide, was obtained in an unusual hydroxylamine elimination and cyclization reaction upon reaction of lb with glutaroddiydroxamic acid (132). Even four distinct hydroxamate binding modes were observed in a heptanuclear Ni(ll) complex with 2-(dimethylamino)phenylhydroxamic acid (2-dmAphaH), [Ni7(2-dmAphaH-l)2 (2-dmApha)g(H20)2]S04- I5H2O (133). 

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