Abstract
Reaction of indole with the combination 1-cyclohexyl-2-pyrrolidinone and phosphoric trichloride gives the hydrochloride of 3-(1-cyclohexylpyrrolidin-2-ylidene)-3H-indole. Treatment of this with base at room temperature causes hydrolytic ring opening producing 4(cyclohexylamino)-1-(1 H-indol-3-yl)butan-1-one but careful low-temperature basification allows the isolation of 3-(1-cyclohexylpyrrolidin-2-ylidene)-3H-indole itself. The crystal structure of the hydrochloride, as a dihydrate, was determined.
Highlights
The reaction of indole with the Vilsmeier reagent[1] (formed using N,N-dimethylformamide (DMF) and phosphoric trichloride), followed by base, is the classic, and very efficient, method for the 3-formylation of indoles[2] (e.g. → 2, Scheme 1) and other electron-rich heterocycles.[3]
When the tertiary cyclic amide 1-methyl-2-pyrrolidinone is utilized under Vilsmeier conditions with indole, 3-(1-methylpyrrolidin-2-ylidene)-3H-indole (5) is the product after base treatment – despite the loss of pyrrole ring aromaticity, the system does not hydrolyze to the amino-ketone (6) (Scheme 3)
We have expended considerable and rewarding efforts on investigations of the properties and reactions of 3-(1-methylpyrrolidin-2-ylidene)-3H-indole (5): we have examined its crystal structure,[9] its UV spectrum and basicity[10], and its intriguing reactivity with 1,3-diketones,[11,12] and malonates.[13,14]
Summary
The reaction of indole with the Vilsmeier reagent[1] (formed using N,N-dimethylformamide (DMF) and phosphoric trichloride), followed by base, is the classic, and very efficient, method for the 3-formylation of indoles[2] (e.g. → 2, Scheme 1) and other electron-rich heterocycles.[3]. When the tertiary cyclic amide 1-methyl-2-pyrrolidinone is utilized under Vilsmeier conditions with indole, 3-(1-methylpyrrolidin-2-ylidene)-3H-indole (5) is the product after base treatment – despite the loss of pyrrole ring aromaticity, the system does not hydrolyze to the amino-ketone (6) (Scheme 3).
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