5.6- Dihydroxy-2-methylindole

In another study (82JOC5258), air oxidation of a-methyl-3,4-dihydroxyphenyl-alanine ethyl ester was shown to lead to ethyl 5,6-dihydroxy-2-methylindole-3-carboxylate 31 via a remarkable 1,2-migration of the ethoxycarbonyl group of the aminochrome intermediate (Eq. (4)). The structure of the product was confirmed by an independent synthesis ... 

Young TE, Babbitt BW, Wolfe LA (1980) Melanin. 2. Electrochemical Study of the Oxidation of a-Methyldopa and 5,6-Dihydroxy-2-methylindole. J Org Chem 45 2899... 

The reduction of adrenochrome (1) with ascorbic acid (59) was first reported in 1948,158 although the nature of the reaction products (which may be of physiological importance, cf. ref. 159) was not determined until several years later. It was shown by Heacock and Laidlaw in 1958 that reduction mixtures of this type contained at least three indolic products,147 one of which was isolated and shown to be 5,6-dihydroxy- -methylindole (28).147 The major component of aqueous adrenochrome-ascorbic acid reaction mixtures has recently been shown to be a secondary product (60) (which was isolated as its di- and tetra-acetyl derivatives) produced by the interaction of the o-dihydroxy group of 28 with the a-dicarbonyl function of dehydro-... 

Reduction of 7-iodoadrenochrome (12) with glutathione gave a complex mixture of products.155 The main product appeared to be chromatographically similar to the glutathione-5,6-dihydroxy- -methylindole complex obtained from adrenochrome (cf. 64B or 65B). However, both the expected 5,6-dihydroxy-7-iodo-lV-methylindole (55) and the corresponding deiodinated product (28) were also detected in the reaction mixture,155 together with a compound which is possibly... 

All attempts to chromatograph epinochrome (in 2% aqueous acetic acid) yielded, in addition to the red epinochrome spot (Rf ca. 0.80), definite spots with Rf s of 0.44 and 0.25 due to the rearrangement product (5,6-dihydroxy-N-methylindole) and an unknown Ehrlich-positive substance, respectively. 

The red color of adrenochrome methyl ether (8) solutions is rapidly discharged on addition of alkali, with the formation of a dirty brown, essentially non-fluorescent, solution from which an unidentified dark grey amorphous product was obtained on acidification,110 possibly 5,6-dihydroxy-3-methoxy- -methylindole (35) and not 5,6-dihy-... 

One of the main products in each case was the expected 5,6-dihy-droxy-7-iodoindole,70,109,119, 1B1,166 which was invariably accompanied by some of the corresponding deiodinated product.1BB (The elimination of the halogen atom in reactions of this type has been referred to previously.109) Reduction of 7-iodoadrenochrome (12) with Na2S204 gives, besides 5,6-dihydroxy-7-iodo-V-methylindole (55) and 5,6-dihydroxy-iV-methylindole (28), the sodium bisulfite... 

Reduction of the 7-iodoaminochromes70 with zinc and dilute acid was usually accompanied by virtually complete elimination of the iodine atom,109,155 except in the case of 7-iodonoradrenochrome (42), where, although the main product was 5,6-dihydroxyindole (29), traces of 5,6-dihydroxy-7-iodoindole (56) were also detected.156 Only partial debromination was observed when 7-bromoadrenochrome (57) was reduced with this system 7-bromo-5,6-dihydroxy-.V-methylindole (58) and 5,6-dihydroxy-iV-methylindole (28) were both obtained in significant quantities.155... 

The main products obtained from the reaction between adreno-chrome (1) and glutathione have been shown to result from the 1,4-addition of glutathione to the C-5 unsaturated carbonyl systems in 1 involving the C6-C7 and the C4-C9 double bonds and are probably [Pg.288]

Dihydroxy-N-methylindole 142 readily reacts with DHA in aqueous solution at room temperature (64CJC1401 65JCS4728) (Scheme 34). The two hydroxy groups of the indole interact with the a-diketone function of DHA to form the 1,4-benzodioxane 144. This type of reaction appears to be general since similar interactions occur between other o-diphenols and a-diketones. The mechanism by which the 1,4-benzodioxane derivative is obtained when adrenochrome 141 is reduced with ascorbic acid to give 142 via 143 was studied. 

The 5,6-dihydroxyindoles, including the parent system 1, are usually white-to-grey crystalline solids that melt with extensive decomposition and darkening. They are soluble in alcoholic solvents and acetone, less in acetonitrile, ethyl acetate, dimethyl sulphoxide (DMSO), tetrahydrofuran (THF), and water, and only sparingly soluble in hydrocarbons, e.g. benzene and light petroleum. A detailed physicochemical characterization of compound 1 was described by Murphy and Schultz (85JOC5873) (85JOC2790). The values for the first and second ionizations of indole 1 were determined as 8.9 and > 10.2, respectively. 5,6-Dihydroxy-1-methylindole 3 has values of 8.4 and 10.7 in water. 

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