Acylhydroxamic acid

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

A formal synthesis of ( )-Eseroline (69) via a 3-aza-4-oxa-Cope rearrangement was reported. An iV-aryl A-hydroxycarbamate was reacted with 2-phenylsulfanylpropanoic acid to yield the O-acylhydroxamic acid derivative 65, R = H that rearranged in the presence of potassium bis(trimethylsilyl)amide. The [3,3] and [3,5] rearrangement products, respectively 66 and 67, were formed (equation 22). If the para-substituted hydroxamic acid 65, R = OCOBu-t is used, no [3,5] rearrangement product is observed and the [3,3] rearrangement product 68 is the only product formed (equation 23). The authors proposed two parallel mechanisms, a concerted pathway and an ionic mechanism by an ion-pair recombination. 

In adequate basic conditions or on heating, activated O-acylhydroxamic acids 73 iso-merize to the corresponding enols 74 to generate an adequate 3-aza-4-oxa-l,5-dienic system suitable for a [3,3]-sigmatropic rearrangement (equation 25). 

Activated A-alkyl-O-acylhydroxamic acid derivatives 75 undergo base catalysed rearrangement to give 2-acyloxyamides 76 in good to excellent yields (50-100%) (equation 26). These precursors of 2-hydroxy amides (77) are good intermediates to prepare ethanol-amines, oxindoles and oxazolidinediones. 

The fourth related rearrangement reaction is the Lossen reaction, which generally occurs by base treatment of 0-substituted hydroxamic acids which possess electron-withdrawing functions at the oxygen atom (e.g. O-acylhydroxamic acids), giving amines via isocyanates (equation 6). Preliminary 0-activation (e.g. O-acylation) of hydroxamic acids is essential for a smooth rearrangement, otherwise it will not occur, ilie Lossen reaction is not as useful as the other three rearrangements since hydroxamic acids are not readily available. 

Tl. J. Gerstein and W.P. Jencks, Equilibria and Rates for Acetyl Transfer among Substituted Phenyl Acetates, Acetylimidazole, O-Acylhydroxamic Acids, and Thiol Esters, J. Am. Chem. Soc., 1964, 86, 4655. 

In an early study on the mechanism of the Beckmann rearrangement, Jones and Hurd showed that the silver salts of JV-acylhydroxamic acids 16 decomposed upon heating in the solid state to produce the corresponding isocyanates 1734. The silver derivative of propane-l,2-diol-3-thiol ( thiovanol ) 18 undergoes thermal decomposition to deposit... 

Aimnoethyl)indoles have been prepared from 3-hydroxy-2-methoxyindolines by way of a Claisen o-amide rearrangement. 0-Acylhydroxamic acid derivatives (82) have been found to undergo a base-catalysed rearrangement to give secondary... 

Fowler and co-workers have studied the participation of 1-acyl-l-azadienes in hetero Diels-Alder reactions, finding that vacuum pyrolysis of the O-acylhydroxamic acid (298) leads to a quinolizine system (300) through an intermediate A-acyl-l-azadiene (299) (Scheme 64), a method that was later applied to the synthesis of several quinolizine alkaloids <83JA7696, 85JOC27i9>. A similar result can be achieved by flash-vacuum pyrolysis of l-acyl-2-azetines <9UOC6729>. 

Most of the above observations and evidence for mechanism ako apply to this reaction of acylhydroxamic acids (reaction 81) ,... 

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