The general acid catalyzed displacement of amines from o-hydroxylaminobenzamides in aqueous and nonaqueous solvents

Abstract

The general acid catalyzed displacement of amines from o-hydroxylaminobenzamides, with formation of 2, l-benzoxisoxazolin-3-one, occurs readily in water and a wide variety of nonaqueous solvents. This, together with the fact that the o-hydroxylaminobenzamides can be obtained simply and quantitatively from the corresponding o-nitrobenzamides by reduction, suggests that amines may be conveniently masked as their o-nitrobenzoyl derivatives. This has been confirmed for some simple amines in preliminary synthetic studies. Kinetic measurements in both aqueous and nonaqueous solvents show that the o-hydroxylamino group strongly promotes the liberation of the amines. In aqueous perchloric acid solutions, for example. the cleavage of o-hydroxylamino-N,N-dimethylbenzamide occurs some 105-106 times more rapidly than the hydrolysis of the unsubstituted N,N-dimethylbenzamide. The mechanism of the reaction is discussed and, in particular, it is suggested that the relatively rapid reaction in solvents such as carbon tetrachloride and benzene can only be accounted for by a one encounter mechanism.The liberation of alcohols from esters of o-hydroxylaminobenzoic acid, with formation of 2,1-benzisoxazolin-3-one (I), has been shown by kinetic' and synthetic studies2 to be I rapid and quantitative in basic solution. The corresponding reaction in acid solution, although considerably slower than in alkaline solution, also shows evidence for direct participation of the hydroxylamino group.' The hydroxylaminobenzoates can be readily prepared from the corresponding o-nitrobenzoates by reduction, and this has led to the proposal* of o-nitrobenzoate as a protecting group for phenols and alcohols.An attempt2 to mask amines as their o-nitrobenzoyl derivatives (Scheme I) was, however, less successful. Thus it was reported that the cyclohexylamide of o-hydroxylaminobenzoic acid (produced by reduction of the o-nitroamide) did not readily liberate cyclohexylamine with base. In an earlier study,3 Cohen and Gray reported rapid cleavage of o-hydroxylamino-N.N-dimethylbenzamide in aqueous alkali, although the yield of the amine was not reported (51% of benzisoxazolinone was recovered). Preliminary work in this laboratory also suggests that, in base solution, the reactions of the amides are not as simple as those of the esters.'q2 However, we have found that the reactions proceed quite rapidly and without complications in acid solutions in both aqueous and nonaqueous solvents.In the present paper, we report a detailed study of the kinetics of the acid catalyzed liberation of amines from the corresponding o-hydroxylaminobenzamides and some preliminary results of a synthetic study on the usefulness of this reaction sequence (Scheme I) for the protection of amines. Experimental SectionMaterials. The nitroamides were prepared according to the procedure of Barton, Coates, and Sammes.2 Reduction of Nitrobenzamides. The nitroamide (3 g) in tetrahydrofuran (THF) (30 ml) was added to a solution of ammonium acetate (8 g) in water (30 ml) and the resultant mix...