Reduction of 2-nitrophenylacetaldehyde gave the unstable 1hydroxyindole, trapped as 1 -acetoxyindole. Concurrent alkaline hydrolysis with methyl iodide present yielded 1 -methoxyindole which was substituted by electrophiles a t position 3. The 3-carbaldehyde, from a Vilsmeier reaction, was converted into 1 -methoxy-NN-dimethyltryptamine. 1.5-Dirnethoxyindole underwent the Mannich reaction forming the 3-dimethylaminomethyl derivative. 1 -Acetoxyindole with dimethylforrnamide and phosphoryl chloride yielded 2-chloroindole-3-carbaldehyde and 1 -hydroxyindole-3-carbaldehyde, while (1 -hydroxyindol-3-y1)glyoxylic acid with hydroxylarnine gave 3-cyano-1 -hydroxyindole or indole-3-nitrile oxide. The u.v., i.r., n.m.r.. and mass spectra of the 1 -hydroxyindole derivatives are discussed.RECENT interest in 1-hydroxyindole derivatives has been stimulated by the isolation from plants of five l-methoxyindole derivatives, 1,5-dimethoxygrarnine [5-Me0-( 8)] ,l 1 -met hox y-NN-dime t h yl t ryp t amine (28), 1 -met hoxyindole-3-acetonitrile (10) ,3 a derivative of l-methoxyindole-3-acetic acid called neoglu~obrassicin,~ and oxaline, the major alkaloid of PeniciZZium oxalicum, which is a complex 2,3-dihydro-l-metho~yindole.~ As secondary aliphatic amines can be oxidised to hydroxylamines by peroxy-acids and in mammals,' the possibility that Nhydroxylation of indoles could occur in vivo needs to be explored, and the biological properties of l-hydroxyand similar analogues of tryptophan, serotonin, etc. can hardly fail to be of interest. An investigation of the synthesis of compounds of these types has therefore been started, syntheses of l-acetoxy-and l-methoxy-indoles have been developed, and the first syntheses of 1,5dimethoxygramine, briefly reported,8 and l-methoxy-NN-dimet hox y trypt amine are described.
RESULTS AND DISCUSSIONl-Hydroxyindole (3) was first obtained by Mousseron-Canet and Bocas by the hydrolysis with sulphuric acid2) (a hydrolysis which has been described as ' tres difficile ' and which we have failed to reproduce), followed by a reliable, carefully controlled reduction with zinc-ammonium chloride. Although