Preparation of the Indole Magnesium Halides

The most widely used procedures for the preparation of the indole magnesium halides are based on the method originally described by Oddo in 1911, and consist of adding a solution of indole or an indole derivative, in dry diethyl ether, to a solution of an alkyl magnesium 

Kharasch and O. Reinmuth, Grignard Reactions of Nonmetallio Substances. Prentice-Hall, F.nglewood Cliffs, New Jersey, 1954. 

Anisole and mixtures of diethyl ether with aromatic hydrocarbons have both been widely employed as solvents for these reactions. Ethers other than diethyl ether and anisole have also been successfully used (cf. refs. 14-17). Hcxamethylphosphorotriamide has recently been used as a solvent for indole Grignard reactions. Young and Mizianty have recently described the use of an aromatic magnesium halide (phenylmagnesium bromide) for the synthesis of indole magnesium bromide. 

Oddo reported that the organomagnesium derivatives of p3Trole, indole, skatole, and carbazole could be prepared in a single operation by mixing the parent heterocyclic compound with an alkyl halide and magnesium in anhydrous ether.The product formed was reported to be the same as that obtained by the more conventional procedure. However, this approach to the synthesis of the indole Grignard reagents does not seem to have been exploited in subsequent work. 

An example of the formation of a Grignard reagent on the benzene ring moiety of the indole nucleus has been described recently. Noland 

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The preparation of indoles by the benzyne route is illustrated by the base-induced cyclization of the amino-alcohols (171 R = H or Me) to indole and 3-methylin-dole, respectively/ The photochemical reaction of o-bromo- or o-iodo-aniline with the enolates (172 R = H, Me, or PrO leads to indoles (173)/ The salt (174), generated by the action of lithium di-isopropylamide on o-tolyl isocyanide, serves as a source of diverse indole derivatives (i) it cyclizes spontaneously to 1-lithioindole, which forms 3-alkyl-indoles on treatment with alkyl halides in the presence of magnesium iodide, (ii) it reacts with allyl esters RC02CH2CH=CH2 (R = alkyl or aryl) to give the ketones (175), which cyclize... 

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