Hydroxamic acids, hydrolysis

Tlnee papers from the same group deal with micellar hydroxamic acid hydrolysis.93 160 161 Micellar effects on the alkaline hydrolysis of (107 R = Ph) were discussed93 earlier. Similar type results are reported in the other two papers.160,161... 

Acid Hydrolysis. With hot concentrated mineral acids, primary nitroparaffins yield a fatty acid and a hydroxylamine salt. If anhydrous acid and lower temperatures are used, the intermediate hydroxamic acid can be recovered. 

R = CH3 and AR = C6H4NO2.) Actually Scheme XXV and Eq. (3-176) both take place, with some of the hydroxamic acid being formed directly and some via the intermediate. (Note that each of these reactions is itself complex, presumably occurring via a tetrahedral intermediate as shown in Scheme XXII for ester hydrolysis.)... 

When the compound for identification fails to respond to test 4 (aldehyde or ketone), the next class reactions to apply are the hydroxamic acid test and saponification, i.e., hydrolysis in alkaline solution. These are the class reactions for esters and anhydrides the rarely-encountered lactones react similarly. 

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.)... 

However, the switchover from an A2 to an A1 hydrolysis is a very common mechanistic pathway in strong acid media, probably more common than the pure A2 mechanism. Excess acidity analyses have shown that thioacetic acid, several thiobenzoic acids, and many thiolbenzoate and thionbenzoate esters show this sort of mechanism switch.179 Acylals and thioacylals also show this behavior,116 with thioacylals using two water molecules and acylals one. Many hydroxamic acids react this way,127,216 as do esters of various types,41,217,218 episulfoxides219 and aryloxatriazoles.220 Acylhydrazines can also show a mechanism switch of this sort, although with these substrates the situation is somewhat more complex.221... 

Other workers4 have recently shown that hydroxamic acid,. R-CONHOH, at pH 7-7 accelerates the hydrolysis of D.F.P. and sarin. They envisage the following reaction, although compound (I) has not been isolated. 

Manecke and his collaborators have synthesized polymers of vinylimid-azole hydroxamic acid (75) (22, 23, 24). Hydrolysis of p-nitrophenyl acetate... 

In an attempt to move away from the hydroxamic acid zinc binding group, which is known to causes poor pharmacokinetics as a result of hydrolysis or glucuronidation, the group at Abbott searched for alternative zinc chelators culminating in the development of a series of electrophilic ketone HDACis (Figure 9.12) [64—66]. Subsequently, a group at IRBM developed a related series of thiophene trifluor-omethyl ketones and showed these to be selective class II HDACis [12]. 

II. HYDROXYLAMINES THROUGH HYDROLYSIS OF HYDROXAMIC ACIDS, OXIMES AND NITRONES... 

Hydrolysis of nitrones, oximes and hydroxamic acids is frequently used as a final step in the preparation of substituted hydroxylamines. Although hydrolysis is the most commonly utilized method for oximes, oxime ethers and nitrones, formation of sensitive hydroxylamines can also be achieved under milder reaction conditions by treatment of... 

Conversion of hydroxamic acids into hydroxylamines is usually performed by hydrolysis or alcoholysis under acidic"" or basic catalysis , although other methods like reaction with trimethylsilyl iodide have also been sparingly used. 

In 1984 Gassman and Granrud, and Novak and co-workers, published their results on reactions of similar esters of hydroxamic acids. Gassman and Granrud showed that the rearrangement of the methanesulfonate esters 45a-g in CDCI3 (Scheme 23) occurred in a first-order fashion and that kobs correlated with with a slope,, of -9.2. Novak and co-workers showed that the pH-independent first-order rate constants for hydrolysis in 5 vol%... 

The mechanism of Scheme 34 quantitatively explains the yields of rearrangement, solvent-derived and N3-derived products of hydrolysis of hydroxylamine or hydroxamic acid esters that yield selective nitrenium ions (log 5 One of the characteristics of these hydrolysis reactions is the... 

Novak and co-workers have examined the hydrolysis reactions of a series of esters, 158a-i, of hydroxylamines or hydroxamic acids that are derived... 

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