Dissolving metals indoles

Indole-2-carboxylic esters undergo reduction with magnesium in methanol to give the 2,3-dihydroindole (indoline). Dissolving metals reduce the heterocyclic ring of isoindoles. 

In addition to the general reviews on indole reduction that were cited above, several reviews and key papers on the dissolving metal reduction of indoles should be consulted for reference to the early work, ... 

The dissolving metal reduction of benzo[b]furans and dibenzofurans is a classical technique and, depending on the conditions, can give rise to a variety of products.Several examples are summarized in equations (104-108). " The cleavage of dibenzofurans to afford 2-hydroxy biphenyls (equation 107) is a particularly valuable route to these compounds. The reduction of 3-carbomethoxybenzofu-rans with Mg/MeOH (equation 108) is reminiscent of the indole reduction reported earlier (equation 51). 

In addition to being more selective, dissolved calcium metal functions in a similar way to lithium and sodium metals towards organic functional groups [45]. Tab. 4.2 lists reductions giving the same products by the three dissolved metals. Among these, calcium affords the highest yields for some substrates (entries 1-3). The compounds in Tab. 4.2 include an aldehyde, indole [46], aryl ketone, enone, naphthalene [47], pyridine N-oxide [48], benzyl alcohol, styrene, and buckminster-fullerene. 

The ready electron availability of indoles means that they are rather easily (aut)oxidised in the flve-membered ring. Reductions can be made selective for either ring in acid solution, dissolving metals attack the hetero-ring, and the benzenoid ring can be selectively reduced by Birch reduction conditions. 

Ethyl indole-2-carboxylate (45.2 g, 0.238 mmol) was dissolved in abs. EtOH (450 ml) in a 11 polyethylene container and cooled in a dry icc-cthanol bath. The solution was saturated with dry HCl gas until the volume increased to 875 ml, Granular tin metal (84.2g, 0.7l0mmol) was added to the slurry and... 

DMA in 500 ml ether mix rapidly with 270 ml 0.9 M phenyl-Li, boil fifteen hours and extract as for (VI) or as described previously to get 8 g oily 4-methoxy-indoline (or its 1-methyl derivative) (VII). Alternatively, add 36 g naphthalene to 300 ml tetrahydrofuran and add 11 g Na metal cut in small pieces. Reflux and stir three hours and add 18 g (VI) and 8 g DEA in 200 ml tetrahydrofuran rapidly and boil twelve hours. Evaporate in vacuum, dissolve the oily residue in 2N HCI and extract with ether. Proceed as described to get (VII). 4 g (VII) in 200 ml dry pyridine add to 6 g Cu chloride in 400 ml pyridine and reflux 1 xh hours. Pour on water and extract with ether. Wash extract with 4N HCI and then water and dry and evaporate in vacuum the ether to get 2 g of the indole (VIII). Alternatively, dissolve 4 g (VII) and 9.5 g cinnamic acid in 700 ml mesitylene, add 1 g 5% palladium-carbon and reflux five hours. Filter, wash with HCI and NaHC03 and dry and evaporate in vacuum the mesitylene to get the red, oily (VIII) (can chromatograph on alumina and elute with benzene-petroleum ether). 

Two problems occur in using acid hydrolysis for quantitative determinations the occurrence of secondary reactions between some of the compounds released by the hydrolysis (phenols, indoles, furans, etc.) and the dissolution of metals (calcium, aluminum, iron), which subsequently precipitate when the solution pH is neutralized. The latter problem could perhaps be overcome by an initial hydrolysis with water in an autoclave (Stefan and Jocteur-Monrozier, 1983), which would dissolve most of the polysaccharides without dissolving the minerals. 

Cyclic voltammetry can be used to show which compounds can be detected by this method and the best potentials to use. Aromatic hydroxy compounds, aromatic amines, indoles, phenothiazines and mercaptans can all be detected oxidatively (with a positive potential). Reductive detection (with a negative potential) is rarely used, as dissolved oxygen and heavy metals (e.g. from steel capillaries) can cause problems. The method can be used for nitrosamines and a large number of pollutants. 

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