Indole Grignard reagents preparation

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. 

Majima et al. prepared ethyl y-(3-indolyl)-y-oxobut3rrate (250) in a similar manner by the condensation of the indole Grignard reagent with -ethoxycarboiiylpropionyl chloride.Methyl y-(3-indolyl)-y-oxobutyrate (251) has been obtained by the action of mcthoxycarbonylpropionyl chloride on indole magnesium iodide in ether. Ballantine et al. prepared methyl y-(5-methoxy-3-... 

Majiina and Kotake prepared 2,2-di(3-indolyl)propane (336) by the action of acetone on indole magnesium iodide in other or anisole. Recently 1 -indolyl derivatives have been o btained as primary products by interaction of ketones with indole Grignard reagents for example acetone gave a 75% yield of 2-(l-indolyl)propan-2-ol (337). 

To the Grignard reagent prepared from 2.4 g Mg, 10 ml anisole and 16 g ethyl iodide, add 7.8 g indole in 10 ml anisole. Stir and cool to 0°. Slowly add dropwise 5.5 g Cl-acetonitrile in 40 ml anisole. Warm to room temperature and stir heat to 60-70° on water bath (a reddish precipitate forms over about twenty minutes). Cool and purify and convert to the dialkyltryptamine as described earlier. Tryptamines JOC 24,894(1959)... 

The Fischer indole synthesis has also been employed. The nitrile (XXXVIII) reacts with the Grignard reagent prepared from y-ethoxy-propyl bromide to give an intermediate (XXXIX) which in the presence of acid generates the cyclic ketone XL. The phenylhydrazone of the last can be cyclized to sempervirine (XXXV) (24). 

Saima confirmed that 132 was readily obtained in ether in the cold. Sanna also prepared 3-bromoacetylindole (133) and 3-iodoacetylindole (134) by the action of bromoacetyl chloride and iodoacetyl chloride, respectively, on the indole Grignard reagent.The corresponding... 

B Add 30 g (II) over one-half hour to 420 ml methyl iodide and let stand fifteen hours at 5°. Separate the iodomethylate which precipitates, dry briefly at 50° and heat with vigorous stirring at 80° for two hours with 60 g NaCN in 1 L water. Extract with CHC13, dry and evaporate in vacuum the extract and dissolve the residue in 250 ml ether. Filter, evaporate in vacuum to a few ml and precipitate the acetonitrile (III) by adding petroleum ether. The acetonitrile can also be prepared directly from the indole via the Grignard reagent as given elsewhere here. 

Kondo employed the Kumada coupling using the Grignard reagents derived from 2- and 3-iodo-l-(phenylsulfonyl)indole to prepare the corresponding phenyl derivatives in 50% yield [92], Widdowson expanded the scope of the Kumada coupling and provided some insight into the mechanism [93],... 

The diketoindoles 777 were prepared in three steps starting from indol-3-ylacetic acid (680) and 5-chloro indol-3-ylacetic acid (774) in 75% and 66% overall yield, respectively. The indole acids 680 and 774 were converted into Weinreb amides 775, followed by reaction with ethyl Grignard reagent to afford the corresponding indol-3-yl ketones 776. In order to introduce the second carbonyl moiety, the 3-substituted... 

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