Hydroxamic acids 805 hydroxides

Ring substituents show enhanced reactivity towards nucleophilic substitution, relative to the unoxidized systems, with substituents a to the fV-oxide showing greater reactivity than those in the /3-position. In the case of quinoxalines and phenazines the degree of labilization of a given substituent is dependent on whether the intermediate addition complex is stabilized by mesomeric interactions and this is easily predicted from valence bond considerations. 2-Chloropyrazine 1-oxide is readily converted into 2-hydroxypyrazine 1-oxide (l-hydroxy-2(l//)-pyrazinone) (55) on treatment with dilute aqueous sodium hydroxide (63G339), whereas both 2,3-dichloropyrazine and 3-chloropyrazine 1-oxide are stable under these conditions. This reaction is of particular importance in the preparation of pyrazine-based hydroxamic acids which have antibiotic properties. 

The action of nitrous acid on o-aminohydroxamie acids gave products that are believed to be triazine hydroxamic acids, e.g., 28. These gave a red color with ferric chloride, and 28 was converted by sodium hydroxide into o-azidobenzoic acid (29). 

Hydroxamic acid complexes, 24 769-770 Hydroxide precipitation, in hazardous waste management, 25 821 Hydroxides... 

Trispyrazolylborates are models for tris-histidine active sites in zinc enzymes, e.g., the matrix metalloproteinases involved in breakdown of extracellular matrices. Inhibition of these metalloproteinases may prove valuable in the treatment of, inter alios, cancer and arthritis, so efforts are being made to find appropriate ligands to block the zinc active site. The search has recently moved on from hydroxamates to hydroxypyridinones - l-hydroxy-2-pyridinone is a cyclic analogue of hydroxamic acid. As reported in Section II.B.2 earlier, hydroxypyridinones form stable five-coordinate complexes on reaction with hydrotris(3,5-phenylmethylpyrazolyl)borate zinc hydroxide. Modeling studies suggest that hydroxypyridinonate ligands should be able to access the active site in the enzyme with ease (110). 

The presence of any of these functional types may be established chemically by applying the hydroxamic acid test. These compounds react with hydroxyl-amine in the presence of sodium hydroxide to form the sodium salt of the corresponding hydroxamic acid. On acidification and addition of iron(m) chloride solution the magenta coloured iron(m) complex of the hydroxamic acid is formed. 

Using two cooled bubblers connected in series and charged with ethanol, 0.5-1 L of air was sampled at a flow of 0.3 L/min. The vinyl acetate was converted to N-hydroxyacetamide by the addition of hydroxylamine hydrochloride and sodium hydroxide. After 30 minutes, the hydroxamic acid was complexed with iron by the addition of hydrochloric acid and ferric chloride. The intensity of the color which developed in 10 minutes was compared to the intensities of standards. The lower limit of detection for this method was reported to be 0.3 yg/mL. 

Beginning in 1946 when it was shown that treatment of acid chlorides of hydroxamic acids with alkali hydroxide gave nitrile oxides (46G148), numerous isoxazole derivatives have been prepared. This method lead to isoxazolo[4,5-d]isoxazoles (equation 31) (59G571). 

The original procedure for the Nef reaction involved the aqueous sulfuric acid hydrolysis of the salts (170) obtained by the treatment of primary and secondary nitroalkanes with sodium hydroxide (equation 30). In contrast, if a neutral primary nitro derivative is treated in hot concentrated mineral acid, the corresponding carboxylic acid (172) is formed via the hydroxamic acid (171 equation 31). This reaction is known as the Meyer reaction and was first described in 1873. Protonation of salts of nitroalkanes occurs preferentially at the oxygen atom to give the aci form (173 equation 32). 

A further example is the Lossen rearrangement, in which an O-acyl derivative of hydroxamic acid, RCONHOCOR, gives an isocyanate on treatment with hydroxide ion, which in turn may be hydrolysed to the amine. Illustrate this reaction pathway. 

Hydroxamic acid halides (a-halooximes) are readily dehydrohalogenated by bases, generating the nitrile oxides. Sodium carbonate or alkali hydroxides,156,222 225 amines,85,225-230 and sodium acetate28 are common... 

When bomeol or camphor is heated with solid potassium hydroxide to 250-280 °C, ring cleavage of the bicyclic system occurs and the product, campholic acid 68, can be isolated in high yield65-67. Thus, (-)-borneol gives ( + )-campholic acid [( + )-68], which has been used as the hydroxamic acid derivative as a chiral ligand for a vanadium catalyst in the enantioselective epoxidation of allylic alcohols (Section D.4.5.2.4.). 

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... 

In e first step of the analysis, up to about 30 mg of the substance to be examined or the prescribed quantity are added 0.5 ml of a 70 g/1 solution of hydroxylamine hydrochloride R in methanol R and 0.5 ml of a 100 g/1 solution of potassium hydroxide R in alcohol R. The solution is heated to boiling. This procedure liberates the alcohol (Figure 3.18.2) and converts the carboxylic acid into a hydroxamic acid (Figure 3.18.3). 

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