Some chemistry of reactive species formed on oxidation of hydroxamic acids

Abstract

Primary and secondary acyl nitroxides [RCON(0)CHR1R2; R = H, R = alkyl and R , R = alkyl] undergo [beta]-H disproportionation to give acyl nitrones [RCON (0 )=CR R] and hydroxamic acids. The acyl nitrones are transient intermediates which have been investigated in this thesis by attempted trapping experiments and by semi-empirical molecular orbital calculations.The known cycloadduct of 1-adamantanecarbonyl nitrone [AdCON+(0 )=CH] and N-phenylmaleimide has been re-investigated and the pivaloyl analogue obtained. Solution pyrolysis of the former does not appear to regenerate the nitrone. Two N-allyl-hydroxamic acids have been prepared, but one-electron oxidation of these gave no evidence for intramolecular trapping of the double bond.Synthesis of N-(primary)alkylhydroxamic acids was achieved in this work by benzoyloxylation (benzoyl peroxide) of the n-alkylamine and modification of the usual reaction conditions to stabilize the N-alkyl-O-benzoylhydroxylamine as the hydrochloride; this circumvents acyl transfer to form amide. The results of a kinetic investigation, using e.s.r., of the second-order decay of the corresponding acyl primary-alkyl nitroxides could not be rationalized solely in terms of the strengths of the B-CH bonds.E.s.r. spectroscopy was also used to study the structure of a stable aroyl t-butyl nitroxide dissolved in a glassy toluenematrix.The M.O. calculations compared the reaction co-ordinates for cycloadditions of acyl nitrones to alkenes with those for similar cycloadditions of simple nitrones. As expected, the activation barriers were lower for the acyl nitrones. This investigation led to a comparison of MNDO and AMI methods of calculation. The former seriously over-emphasises core-core repulsions near the transition state. This is clearly demonstrated by a difference map of energy surfaces obtained by the two methods.The stilbene derivative, N-t-butyl-O-B-styrylbenzohydrox-amic acid has been prepared in order to compare the rate of intramolecular addition of the derived nitroxide to the stilbene double bond with the rate of intermolecular addition of a model nitroxide to trans-stilbene. The results of the kinetic measurements gave an effective molarity of ca. 5 x 10 M, in marked contrast to values of only ca. 1-100 M for intramolecular hydrogen abstraction by acyl nitroxides.