Nitroso compounds reduction, hydroxylamine synthesis

Reductive alkylations have been carried out successfully with compounds that are not carbonyls or amines, but which are transformed during the hydrogenation to suitable functions. Azides, azo, hydrazo, nitro and nitroso compounds, oximes, pyridines, and hydroxylamines serve as amines phenols, acetals, ketals, or hydrazones serve as carbonyls 6,7,8,9,12,17,24,41,42,58). Alkylations using masked functions have been successful at times when use of unmasked functions have failed (2). In a synthesis leading to methoxatin, a key... 

The reduction of aromatic nitro compounds is believed to proceed to an intermediate mixture of nitroso compounds and substituted hydroxylamines which are not isolated but condense to form an azoxy compound which, in turn, is reduced to an azo compound. Contributing evidence to substantiate this mechanism is that the reduction of a mixture of two aromatic nitro compounds leads to a mixture of azo compounds consistent with that predicted if each of the nitro compounds were reduced to a nitroso compound and a hydroxylamine and these, in turn, reacted with each other in all possible combinations. This observation also implies that the bimolecular reduction of nitro compounds is practical only from the preparative standpoint for the production of symmetrically substituted azo compounds. Spectrophotometric studies of the reaction kinetics of the reduction of variously substituted nitro compounds may, however, uncover reasonable procedures for the synthesis of unsymmetrical azo compounds. 

Methods for the reductive cleavage of the N—O bond in hydroxylamines have assumed increasing importance in synthesis because it is a key step in routes based on cycloaddition of nitrones and nitroso compounds. Inter- and intra-molecular cycloadditions of nitrones lead to the formation of tetrahydroisox-azoles (Scheme 25) these compounds are then converted into amino alcohols by reductive cleavage of the N—-O bonds. This type of reaction sequence has been exploited in the synthesis of a number of alkaloids.Nitroso compounds, particularly those activated by electron-withdrawing substituents, act as dienophiles in the Diels-Alder reaction (Scheme 26) and the cycloadducts can be used as synthetic intermediates by cleaving the N—O bonds. 

Methods for preparation of hydroxylamine derivatives have been reviewed in detail recently. Here, mainly new developments concerning the synthesis of hydroxylamines by substitution processes with heterobond formation are presented. Reduction of nitro, nitroso, oxime and nitrone derivatives as well as direct oxidation of amines leading to hydroxylamine compounds will not be considered. 

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