Nucleophilic Substitution Reaction on the Nitrogen of Indole Nucleus: Formation of 1-(Indol-3-yl)indoles upon Reaction of 1-Hydroxyindoles with Indole in Formic Acid

Abstract

1-(Indol-3-yl)indoles are obtained in excellent to good yields by the reaction of 1-hydroxyindoles with indole in 85% formic acid.Their structures are determined by X-Ray crystallographic analysis and chemical correlations.The unprecidented SN2 mechanism on the indole nitrogen is proposed.In this communication, 1 we wish to report a formation of 1-(indol-3-yl)indoles (2a-c) upon reaction of 1-hydroxyindoles 2 (1a-c) with indole in 85% HCOOH (Scheme 1).A typical procedure is as follows: 85% aqueous HCOOH was added to a mixture of N,N-dimethyl-1-hydroxyindole-3-acetamide (1a) and indole (10 mol eq), and stirring was continued at room temperature for 2 h.After addition of H 2 O to the reaction mixture, the whole was extracted with 5% MeOH-CHCl 3 .The extract was washed with brine, dried over Na 2 SO 4 , and evaporated under reduced pressure to leave an oil which was column-chromatographed to give 2a and 3a in 84 and 8% yields, respectively.From the reaction mixture, 4, 3 5, 4 and 6, 4 products originated from an excess amount of indole, were also isolated in the respective yields of 1, 11, and 37%.Under similar reaction conditions, 1 b provided 2 b and 3 b in 55 and 9% yields, respectively, while 1c afforded 2 c and 3 c in the respective yields of 47 and 9%.In both reactions, concomitant formations of 4, 5, and 6 were observed as well.Chemical correlations among 1-(indol-3-yl)indoles (2a-c) were readily attained by the following sequence of reactions.Thus, hydrolysis of 2b with sat.aq.NaHCO 3 provided tryptamine (2 d) in 99% yield.Methoxycarbonylation of 2 d with methyl chloroformate in the presence of Et 3 N afforded 99% yield of 2 c, which was identical with the sample obtained from 1 c.Dimethylation of 2 d with HCHO and NaBH 3 CN smoothly proceeded to give 92% yield of dimethyltryptamine (2 e), which was identical with the sample prepared in 76% yield by the reduction of 2a with LiAlH 4 in THF.Compound (2a) was suitable prisms for X-Ray single crystallographic analysis.The results shown in